Proceedings of the 1st International Conference for Cancer Metabolism and Therapy, October 14-17, 2016, Dalian, China.

The first International Conference for Cancer Metabolism and Therapy was held in Dalian, China from October 14 to October 17, 2016 at the New World Hotel. The conference was organized by Dalian University of Technology with sponsorship from the chemical engineering and environmental-biological schools, Dalian University of Technology and the Hirshberg Foundation for Pancreatic Cancer (http://pancreatic.org/) and participating industries, Illumina, Agilent, Beijing Ancomol Biotechnologies Co Ltd, Beijing Xinyang Technology Development Co Ltd, Dalian Haoyun Science and Technology Co Ltd, and Chongqing Hichuang Biological Co. The goals of the conference were to invite national and international experts to present and discuss precision medicine focused on cancer metabolism and therapy. Cancer metabolism is intimately linked to drug resistance, which is currently one of the most important challenges in cancer therapy. Recent advancement of novel high-throughput technologies, such as genomics, transcriptomics, proteomics, metabolomics, phenomics, and mega-data bioinformatics (core technology of precision medicine), has been significantly enhanced our understanding of metabolic properties related to malignancy, paving the way for development of biomarker used for early diagnosis and prognosis of cancer, and effective selection of molecular targets for therapeutic interventions. As the burden of cancer is rampantly increasing and posing challenges in early diagnosis and treatment, this is identifying the genuine need in the area and its implementation for patients. The conference covered a wide range of topics in cancer such as etiology, epidemiology, metabolic reprogramming, environment altered i.e. surgical therapy, chemotherapy, and radiotherapy, and cancer stem cell therapy. Currently, cancer therapy and research are in a new era of rapid and significant developments not only in the West but also in Asia as well. Due to newly developed technology, we can now readily use many high-tech diagnostic tools, new anticancer drugs, molecular targeting chemotherapy, less invasive and/or less expensive and effective therapy that were unavailable in the near past. Therefore, it is crucial for scientists from all over the world to get together and to share your new ideas and thoughts with each other, especially for young scientists from all over the world who can communicate openly with the global leaders in the field, investigators, medical and surgical oncologists through your presentations and vigorous discussion. This conference has achieved its goals and will help bring about substantial advances in both cancer research and improvement in therapy for all cancer patients. The next meeting is planned to be held October 13–October 16, 2017 in Wenzhou, Zhejiang, China. The meeting venue will be in Wenzhou Dynasty Grand Hotel, Zhejiang, China. Abstracts Presented by Various Speakers Novel Ion Chromatography With Mass Spectrometry: Global and Targeted Metabolomic Analysis of Cancer Cells S. Hu. University of California, Los Angeles, Los Angeles, CA. Background: We have recently developed a powerful methodology, based on capillary ion chromatography (Cap IC) with Q Exactive mass spectrometer, for metabolomic analysis of cancer cells. The Cap IC allowed an excellent separation of polar metabolites, and the sensitivities increased by up to 100-fold compared to reversed-phase liquid chromatography and hydrophilic interaction chromatography. The detection limits for a panel of standard metabolites were between 0.04 to 0.5 nmol/L (0.2 to 3.4 fmol) at a signal-to-noise ratio of 3. Method: This platform was applied to a global metabolomic analysis of head and neck cancer cells and stem-like cancer cells. Differential metabolomics analysis identified significant changes in energy metabolism pathways (e.g., glycolysis and tricarboxylic acid cycle). Results: These studies indicate that Cap IC/MS is a powerful metabolomics tool by providing enhanced separation and sensitivity of polar metabolites combined with high resolution and accurate mass measurement (HR/AM) capabilities to differentiate isobaric metabolites. We have also demonstrated a targeted metabolomics method for analysis of cancer cells, based on high-performance ion chromatography (IC) separation, Q Exactive HF MS for HR/AM measurement and the use of stable isotope-labeled internal standards for absolute quantization. Our method offers great technical advantages for metabolite analysis, including exquisite sensitivity, high speed and reproducibility, and wide dynamic range. The high-performance IC provided fast separation of cellular metabolites within 20 min and excellent resolving power for polar molecules including many isobaric metabolites. The IC/Q Exactive HF MS achieved wide dynamic ranges of 5 orders of magnitude for six targeted metabolites, pyruvate, succinic acid, malic acid, citric acid, fumaric acid, and alpha-ketoglutaric acid, with R2 ≈ 0.99. Using this platform, metabolites can be simultaneously quantified from low fmol/μL to nmol/μL levels in cellular samples. The high flow rate IC at 380 μL/min has shown excellent reproducibility for a large set of samples (150 injections), with minimal variations of retention time (SD < ± 0.03 min). In addition, the IC-MS-based approach acquires targeted and global metabolomic data in a same analytical run, and the use of stable isotope-labeled standards facilitates accurate quantization of targeted metabolites in large-scale metabolomics analysis. Conclusion: This metabolomics approach has been successfully applied to analysis of targeted metabolites in head and neck cancer cells as well as CSCs, and the findings indicate that the metabolic phenotypes are distinct between high and low invasive head and neck cancer cells and between CSCs and non-SCCs. High Content Imaged Based Screening for Identification of Novel Treatments and Personalized Medicine for Leukemia S. Oppermann, J. Ylanko, Y. Shi, D.E. Spaner, D.W. Andrews. Biological Sciences, Sunnybrook Research Institute, Toronto, Canada. Background: Current cancer therapy is generally prescribed on a “one size fits all” basis without ensuring that the prescribed treatment will be effective for an individual’s cancer. While it has become clear that cancer is unique to each individual. Ideally we would like to be able to identify a unique combination of effective drugs for an individual patient, and improve the outcomes of treatments for advanced forms of cancer. Method: Using Chronic Lymphocytic Leukemia (CLL) as a disease model, we are establishing imaged based screening techniques for personalized cancer treatment decisions and drug-response monitoring. Circulating tumor cells from peripheral blood of individual patients are stimulated in culture to recapitulate the highly treatment-resistant tumor microenvironment and then used to screen libraries compounds by fluorescence assays for cell death. Results: We show that conventional drugs for CLL that are effective in killing circulating cancer cells, including the recently FDA approved drugs Venetoclax, Ibrutinib and Idelalisib are not effective in killing stimulated proliferating cancer cells. The mechanism of action of Venetoclax is unique in that it kills cells by inhibiting anti-apoptotic proteins to provoke permeabilization of the mitochondrial outer membrane. We hypothesized that the microenvironment of CLL cells in proliferation centers, such as the spleen and bone marrow, provides signals to the cells that prevent them from dying in response to inhibition of anti-apoptotic proteins. We reasoned that inhibitors of kinases might prevent these survival signals from conferring resistance and thereby restore killing of CLL cells by Venetoclax. Conclusion: Our results demonstrate that using image based high content screening it is possible to identify kinase inhibitors that overcome drug resistance in stimulated CLL cells and to assess drug sensitivities for individual patients. Based on the CLL paradigm similar strategies and techniques could be used for AML and for solid tumors in which signals from the microenvironment contribute to survival. Our results suggest that for many cancers it should be feasible to use robotic screening of compound libraries to identify effective, individualized drug combinations for patients. Targeting MEK/ERK Signaling in Rheb-Y35N Driven Cancers Y. Liu. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. Background: Rheb is a Ras family GTPase, which binds to and activates mammalian target of rapamycin complex 1 (mTORC1) when GTP loaded. Recently, cancer genome sequencing efforts have identified recurrent Rheb Tyr35Asn mutations in kidney and endometrial carcinoma. Results: Here we show that Rheb-Y35N causes not only constitutive mTORC1 activation, but sustained activation of the MEK-ERK pathway in a TSC1/TSC2/TBC1D7 protein complex and mTORC1-independent manner, contributing to intrinsic resistance to rapamycin. Rheb-Y35N transforms NIH3T3 cells, resulting in aggressive tumor formation in xenograft nude mice, which could be suppressed by combined treatment with rapamycin and an extracellular signal-regulated kinase (ERK) inhibitor. Furthermore, Rheb-Y35N inhibits AMPKα activation in response to nutrient depletion or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), leading to attenuated phosphorylation of BRAF-S729 and retained mitogen-activated protein kinase (MAPK) activation. Finally, we demonstrate that Rheb-WT can bind AMPK to facilitate AMPK activation, whereas Rheb-Y35N competitively binds AMPK, impairing AMPK phosphorylation. Conclusion: In summary, our findings indicate that Rheb-Y35N is a dominantly active tumor driver that activates both mTORC1 and MAPK to promote tumor growth, suggesting a combination of mTORC1 and MAPK inhibitors may be of therapeutic value in patients whose cancers sustain this mutation. Cancer Metabolism and Beyond Z. Lu. MD Anderson Cancer Center, Houston, TX. Background: We have identified aberrant regulations of metabolic enzymes, which are critical for tumor progression. Pyruvate kinase M2 (PKM2) has been demonstrated to act as a protein kinase to regulate gene expression, G1-S transition, mitosis, and cytokinesis. Results and Discussion: PKM2 protein kinase activity plays an instrumental role in regulation of the Warburg effect by upregulation of glycolytic gene expression. The Warburg effect is coordinately regulated by phosphoglycerate kinase 1 (PGK1), which translocates into mitochondria and function as a protein kinase to suppress mitochondrial pyruvate metabolism for enhanced aerobic glycolysis. In addition, the multiple roles of metabolic enzymes in cancer development are also evidenced by fructose kinase A, which functions as a protein kinase to regulate DNA and RNA synthesis for tumor cell proliferation. These studies systematically reveal the mechanisms underlying the Warburg effect and the metabolic and non-metabolic roles of metabolic enzymes in the regulation of cancer cell metabolism and cell cycle progression. Conclusion: The discoverers of tumor-promoting functions of metabolic enzymes provide novel approaches for diagnosis and treatment of human cancer. C-Myc Regulation of Cellular Metabolism P. Gao. School of Life Sciences, University of Science and Technology of China, Hefei, China. Background: One of the emerging hallmarks of cancer has been the deregulated cellular metabolism, which is well beyond the Warburg Effect, or the aerobic glycolysis, as Otto Warburg described some 90 years ago. Now it is well established that many oncogenes such as Ras, Myc, HIF1, Akt and tumor suppressors like P53 and PTEN are largely behind the deregulated metabolism in cancer cells. Results and Discussion: In this presentation, I will discuss our recent evidence regarding how oncogene Myc regulates metabolism of glucose and glutamine in cancer cells as well as in stem cells. Conclusion: In particular, our recent results will show some novel mechanistic insights into how Myc regulates cellular metabolism and gene transcription in general. Activation of AMPKα by Metformin Inhibits the Expression of CD39 and CD73 on Myeloid-Derived Suppressor Cells via Modulation of HIF1α Signaling in Ovarian Cancer L. Li. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Background: Metformin has been reported to have anti-cancer effects as a prescribed drug for type 2 diabetes. However, the underlying mechanism is poorly known. We show in this study that AMPKα activation and HIF1α inhibition by metformin exerts an indirect immune-mediated, antitumor effect through inhibition of MDSC-mediated immunosuppressive mechanisms. Because metformin administration inhibited MDSC activity and was associated with restored T-lymphocyte activity, we reasoned that it may create a favorable environment for effective immunotherapy. Method: We document for the first time that a fraction of MDSCs from patients with ovarian cancer (OC) expresses CD39 and CD73 to inhibit CD8+T cell activities of producing IFN-γ, Granzyme-B and Perforin, and can be reversed by the effect of metformin. Results: Our study provides the strong evidence showing CD39 and CD73 as prospective functional markers defining myeloid-derived suppressor cells (MDSCs) and the ectoenzymatic activity of CD39 and CD73 is required for MDSC-mediated suppressive. Conclusion: Metformin may recover tumor-induced immunosuppressive mechanisms and invoke a measurable antitumor immune response that delays cancer progression. Essential Roles of Mitochondrial Lon Protease in Regulating Cancer Cell Growth and Cellular Bioenergetics L. Lan,* K. Huang,† Y. Liu,* B. Lu*. *Protein Quality Control and Diseases Laboratory, School of Life Sciences, Wenzhou Medical University, Wenzhou, China; †Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Background: Mitochondria play a primary role in cellular bioenergetics in most eukaryotic cells, which are responsible for producing nearly 95% of cellular ATP through mitochondrial oxidative phosphorylation as well as the control of cell death or survival. Protein homeostasis within mitochondria matrix is essential for the tumor viability, which is controlled precisely by the protein quality control systems including three highly evolutionarily conserved ATP-dependent proteases. As one of the three ATP-dependent serine protease located in mitochondrial matrix, Lon contributes to the degradation of abnormal proteins including misfolded, misassembled, aggregated or damaged proteins, as well as the maintenance of mitochondrial genome (mtDNA). The involvement of mitochondria in cell death implies its critical role in probing the cellular sensitivity to anticancer drugs. Lon is an ATP-dependent serine protease with multi-functional enzyme and highly conserved from bacteria to mammalian mitochondria and peroxisomes. Although the majority of Lon is soluble within the mitochondrial matrix, it is also found in mitochondrial nucleoids with the roles in mtDNA maintenance. Lon is a stress protein and can be induced by a number of stresses such as accumulation of unfolded proteins in endoplasmic reticulum(ER), hypoxia and other stress conditions. The Lon up-regulation may be critical for cancer cell survival by preventing abnormal mitochondrial proteins accumulation and aggregation in response to oxidative, hypoxic, and ER stress Results: Our recent studies demonstrated that Lon expression was increased in cervical cancer tissues and Lon may serve as a potential therapeutic target in cervical cancer. Previous studies showed that Lon protease were up-regulated in human lung cancer cells and malignant B-cell lymphoma cells. Our recently published work shows that anti-cancer drug bortezomib can block the TFAM degradation and increase mtDNA copy numbers in cells with extremely low mtDNA by inhibiting Lon protease activity. In human oral cancer cell OEC-M1 and FADU, over-expression of Lon protease resulted in the enhancing of mitochondrial ROS generation, which is related to Lon-mediated up-regulation of a mitochondrial Fe-S protein in complex I of electron transport chain (NDUFS8). Here, our knocked down Lon and found drastically reduction of cancer cell proliferation and cell growth. The mtDNA encoded subunit II of COX was degraded rapidly and the steady-level of nuclear-encoded Subunit IV and V of COX were also reduced under ER stress. During hypoxia, hypoxia inducible factor 1 (HIF-1) activates the LON gene transcription which up-regulates Lon protease expression. Increased Lon protease degrades COX4-1 (isoform 1 of COX subunit 4) to facilitate the switch from COX4-1 to more efficient COX4-2 to challenge the low oxygen by enhancing mitochondrial respiration. Thus, Lon protease mediated protein degradation can relieve the heavy load of abnormal mitochondrial proteins accumulation caused by ER stress and /or oxidative stress. Maintenance of energy homeostasis is critical for cell proliferation, survival, differentiation and apoptosis. Our results showed significantly decrease of cellular energy metabolism. Moreover, down-regulation of Lon decreased mitochondrial ROS production and blocks c-Jun N-terminal kinases (JNK) activation, which suggest that down-regulation of Lon reduce ROS production in bladder cancer cells. So we proposed that these would due to that down-regulation of Lon protease leads to the impairment to the assembly and/or function of mitochondrial respiratory chain complexes and inhibits the mitochondrial ROS production, and decreased ROS level inhibits cancer cell proliferation, cell survival. Consistently, we found more vacuolization, fission and a strikingly decrease of cristae abundance in Lon knock down group. Taking the properties of Lon into account, we constructed Lon knockout mice to further confirm our data. Surprisingly, Lonp1deletion causes embryonic lethality which indicated that Lon may play crucial role in embryonic development. Further work would focus on validate the mechanism of this issue. Additionally, we demonstrated that Lon alteration modulates cell survival via selectively degrades mitochondrial located p53which endows the anti-apoptotic ability of cancer cells. And we also found Lon was dramatically increased in bladder cancer, lung cancer, esophagus cancer and cervical cancer. Moreover, patients within high Lon level have much poor outcomes. Conclusion: Together, we suggest that Lon could serve as a potential diagnostic biomarker and therapeutic target for cancer treatment. Pancreatic Cancer Research Gaps and Opportunities V.L.W. Go. Agi Hirshberg Center for Pancreatic Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA. Background: Pancreatic ductal adenocarcinoma is the predominant histologic type in sporadic (approximately 90% of patients) and familial (approximately 7% of patients) cancer of the pancreas (PC). In the United States, pancreatic cancer is the fourth leading cause of cancer related deaths with a 5 year relative survival rate of only 6%. Without significant advances in early detection and treatment, PC is estimated to become the second leading cause of cancer death by 2020. Results and Discussion: Recent genomics breakthrough analysis has identified 4 distinct tumor subtypes, squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX), with its histopathological characteristics and differential outcome. i) This new knowledge is critical to the development of precision medicine with potential in development appropriate biomarkers for early diagnosis and possible to customize treatment approaches for individual patients. Significant progress is now known in pancreatic carcinogenesis including critical events in the reprogramming from acinar to ductal to pancreatic ductal adenocarcinoma to acinar cell demonstrating the plasticity of pancreatic cancer. This concept of reprogramming cancer cells to benign counterpart provides a therapeutic opportunity. To move the field forward, the greatest need is to identify challenges through a gap analysis across disciplines, integrate knowledge, and establish partnership opportunities. ii) The strategic map for innovation and research direction has recently established with the USA-National Institute of health through the formation of the pancreatic cancer center consortium iii) to address the issue related to the high risk group of patients with chronic pancreatitis, diabetes, and pancreatic cancer and to develop a multidisciplinary group to coordinate, provide a framework and to identify other opportunities for pancreatic cancer research. iv) An offering of earlier diagnosis and therapy, a better prognosis and improved quality of life and longer life expectancy for patients with PC is the ultimate goal. Expression of MALAT1 in Endometrial Carcinoma and Endometriosis and Its Significance T. Shi. Faculty of Laboratory Medicine, Xiangya Medical College of Central South University, Changsha, China. Background: MALAT1 plays an important role in various types of cancers. Although endometriosis is a benign lesion, it shows the biological behavior of the malignant tumor. To study the expression of MALAT1 in endometrial carcinoma and endometriosis will bring new ideas to clinical treatment of endometriosis. Method: 40 cases of ovarian chocolate cyst, 43 cases of endometrial carcinoma and 30 cases of healthy controls. The expression level of MALAT1 in ectopic endometrial tissues of endometriosis, endometrial carcinoma tissues, endometrial tissues of healthy controls and the whole blood and serum in these three groups were detected by real-time PCR. Results: (1) MALAT1 was expressed in ectopic endometrial tissues of endometriosis, endometrial carcinoma tissues. The whole blood and serum in these two groups could also express MALAT1. (2) The MALAT1 expression level in ectopic endometrial tissues of endometriosis, endometrial carcinoma tissues of endometrial carcinoma were significantly lower than that in healthy controls (P <0.05). The same results appeared in whole blood and serum. (3) The MALAT1expression level in endometrial carcinoma tissues of endometrial carcinoma was significantly lower than that in ectopic endometrial tissues of endometriosis (P<0.05). The same results appeared in whole blood and serum. Conclusion: MALAT1 express lower in tissues, whole blood and serum of patients with endometrial carcinoma and endometriosis. MALAT1 may be an important mediator of chronic inflammation-tumor transition. Nucleo-cytoplasmic Shuttling Protein FMRP Promotes STAT3 mRNA Localization to the Cellular Protrusions and HCC Metastasis Z. Shen. Wenzhou Medical University, Wenzhou, Zhejiang, China. Background: Cancer cell motility plays a key role in spreading tumors throughout the human body, a process known as tumor metastasis. Cellular motility requires the formation of protrusions, or pseudopods, at the leading edge of the cell. These protrusions are highly polarized structures, enriched in cytoskeletal proteins, adhesion proteins, integrins, signaling factors, translation factors and other proteins. The studies have suggested that the targeting and accumulation of the transcripts coding for these proteins within the pseudopodial extensions lead to their local translation, which required for tumor metastasis. Results and Discussion: Our studies have shown that the mRNA encoding the Stat3 (signal transducer and activator of transcription 3) was identified to localize only at protrusions of hepatocellular carcinoma (HCC), also protrusion localization of Stat3 protein. Importantly, protrusion-localized Stat3 interacts with pseudopod-enriched platelet-derived growth factor receptor tyrosine kinase (PDGFRTK) in a growth factor-dependent manner. STAT3 exists in two isoforms generated by alternative splicing, the full length STAT3 alpha and the truncated STAT3 beta, generally thought to act as a dominant negative factor. However, only STAT3 α can be detected at the protrusions of HCC cells. STAT3 mRNA contains the 3’-UTR which is required for localization to the protrusions of cells. Interestingly, IP-RT-PCR has shown that Fragile X Mental Retardation Protein (FMRP) interacts with STAT3 mRNA 3’-UTR. Deletion of 3’-UTR or knock-down of FMRP using siRNA disrupts the proper localization of STAT3 mRNA at the protrusions, and decreases drastically the metastasis and invasion of liver cancer cells. Conclusion: Our research explores the role of mRNA localization at protrusions in cancer cell metastasis and the possibility that the localization of specific transcripts may help drive or sustain metastasis in some cancers. High Circulating IGF-1 Levels as a Risk Factor in the Accelerated Tumor Growth in Obese Mice S. Wang, J. Wu, X. Liu, N. Wang, Y. Li, M. Guo, R. Jiang, B. Liu, X. Liu, J. Sun, L. Ran, Y. Wu. Dalian Medical University, Dalian, China. Background: We previous showed the chronic IGF-1 gene specific deficiency in the liver mice (LID) that IGF-I mRNA expression was completely abolished in liver. However in extrahepatic tissues like fat, spleen, heart, muscle or kidney IGF-I mRNA was similar to controls. In circulation there was a 75% reduction in Igf-I levels in LID mice. Method: We used the LID mice to study the importance of IGF-I in mammary carcinoma and we induced mammary tumors using the DMBA carcinogen and the SV40 LTA transgene. In both cases there was a delay in tumor appearance in the LID mice compared to controls. In the DMBA models we observed increased squamous metaplasia in control mice as compared to LIDs and in the SV40-LTA tumor volume were significantly increased in controls as compared to LID mice. Serum levels of IGFBP3 which is the major binding protein of IGF in circulation are dramatically decreased. Results: Obese mice had a heightened inflammatory response in the liver. Among the mechanisms implicated in the tumor-promoting effects of obesity, signaling by insulin-like growth factor-I (IGF-I) and insulin has received considerable attention. However, the emerging realization that obesity is associated with chronic inflammation has prompted other consideration of how the IGF-I axis may participate in cancer progression. We used two mouse models of chronic (LID) and inducible (iLID) IGF-1 gene specific deficiency in the liver to investigate the role of IGF-I in regulating the host microenvironment and colorectal carcinoma growth and metastasis in obese mice. Conclusion: In the setting of obesity, our findings imply that IGF-1 is critical to activate and sustain an inflammatory response in the liver that is needed for hepatic metastasis, not only through direct, paracrine effect on tumor cell growth, but also through indirect effects involving the tumor microenvironment. The Role of Dicer in Carcinogenesis K. Tang. Digestive Cancer Center, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Background: Dicer is the key enzyme of the RNAi pathway and is down regulated in most tumor tissues, knockout of Dicer in hepatocytes led to spontaneous HCCs. We proposed that decreased Dicer expression is critical for carcinogenesis. Method and discussion: Here, I will address the molecular mechanism underlying why Dicer downregulation lead to tumor development. Firstly, Dicer is essential for the maintenance of genome stability, decreased Dicer expression causes DNA damage, which may induce gene mutation and lead to carcinogenesis. Secondly, Dicer interacts with SIRT7 and holds a proportion of SIRT7 in the cytoplasm, decreased Dicer expression leads to H3K18 hypoacetylation upon DNA damaging. H3K18 deacetylation is critical to the maintenance of oncogenic transformation. Therefore, Dicer may participate in carcinogenesis via regulating H3K18deacetylation. Thirdly, Dicer processes 7SL RNA into small fragments, which function as dominant-negative regulators of the full-length 7SL RNA, and interfere with signal recognition particle (SRP) complex formation. Decreased Dicer expression enhances SRP-mediated protein targeting, and increases hepatitis B surface antigen (HBsAg) secretion. HBsAg repress MICA and MICB expression via induction of cellular miRNAs in HCC cells. Conclusion: Dicer may participate in antitumor immune response. Fourthly, Dicer may regulate tumor development via different miRNAs α-catenin, a Tumor Suppressor in Cancer Progression H. Piao. Scientific Research Center for Translational Medicine, Division of Biotechnology, Dalian Institute of Chemical Physics, Dalian, China. Background: α-catenin is one of the core components of the E-cadherin-catenin complex and is required for maintaining the integrity of the intercellular adherens junction, a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. Therefore, loss of α-catenin can result in loss of cell-cell adhesion, a common characteristic of cancer cells. α-catenin is a putative tumour suppressor in myeloid leukaemia, glioblastoma and skin cancer. There is an emerging recognition; however, that α-catenin also regulates multiple signaling pathways independent of adherens junctions. For instance, α-catenin regulates Wnt/β-catenin, and Hippo-YAP pathways in glioblastoma, skin cancer. Also α-catenin functions as a tumor suppressor in E-cadherin-negative basal like breast cancer cells by inhibiting NF-KB signaling. Conclusion: α-catenin regulates distinct signaling pathways depending on the tissues type and the surrounding microenvironment, future studies should determine the specific α-catenin signaling pathways in different human cancer types and subtypes, and should evaluate its implication in cancer diagnosis, prognosis and treatment. Application of Tracer-based Metabolomics in the Study of Cancer Metabolism W.N.P. Lee. Biomedical Mass Spectrometry and Metabolomics Core at Harbor-U