P11 KRT17 PROMOTES PROLIFERATION AND METASTASIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA LEADING TO POOR PROGNOSIS

Abstract Background Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found overexpression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remain indistinct. Methods We verified the expression of KRT17 in ESCC tissues by Western blotting and q-PCR. And then the immunochemistry was performed to investigate the KRT17 expression in 64 ESCC tissue specimens. KRT17 upregulated, and knockdown EC9706 and Eca109 cells were constructed by Lentivirus overexpression and CRISPR-Cas9. The function of KRT17 in ESCC proliferation and metastasis were studied by CCK-8 assays, plate colony formation assays, trans-well and wound healing in vitro. Results overexpression of KRT17 was verified in 12 pairs of fresh ESCC tissues. We found that the expression of KRT17 was remarkably positively correlated with the depth of invasion (T) (P<0.05), lymph node metastasis (N) (P<0.05), tumor node metastasis (TNM) stage (P<0.0001). High expression of KRT17 predicted a lower 5-year survival rate(P<0.001) of ESCC patients. We verified the KRT17 malignant behavior of ESCC in vitro. We conformed proliferation and migration capacity of ESCC were significantly enhanced by overexpression of KRT17 but compromised when KRT17 was knocked down. Collectively, it supported that the increased expression of KRT17 promoted proliferation and migratory phenotype of ESCC. Conclusion The breakthrough indicated that the upregulation of KRT17 in ESCC is closely related to malignant progression, our findings revealed that KRT17 plays a vital role in facilitating proliferation and metastasis, and could be used as a novel predictive biomarker, thus providing a novel diagnosis and therapeutic target for ESCC patients. Keywords: Molecular target ESCC Keratin17 Therapeutic target