MUC13 interacts with SOX2 leading to cell sternness and Anoikis resistance in colorectal cancer

Colorectal Cancer(CRC) is one of the leading cause of cancer related death in the United States today in both men and women. With an expected 50,260 deaths in 2017 it is the second leading cause of cancer related deaths among men and the third among women in the United states. Often in colorectal cancer it is not the primary tumor that is the killer, but it is the metastatic sites that develop in the later stages of the disease that is the true killer. About 90% of all cancer related deaths are due to the development of metastatic sites in the body. What is metastasis? Metastasis is the transfer of disease from the primary tumor site to another unconnected site within the body through a process called the metastatic cascade. Metastasis develops slowly over time, due to it being an inefficient process having to overcome several natural defenses within the body. One of these defenses is Anoikis, cell death due to lack of attachment to the extracellular matrix. The development of Anoikis resistant is key in the process of metastasis, because of the need of the cells to detach and circulate the body before settling at a new site within the body. The inhibition of Anoikis resistance development in CRC could lead to improve patient outcome and the failure of metastasis to develop in the lifetime of the disease in the patient. Thus, characterizing and developing methods of inhibition of Anoikis resistance could lead to the decrease in cancer related deaths in the United States as well as finding effect therapeutic options. One of the key characteristics of Anoikis resistance in cells is the develop of stem cell like characteristics, and expression of key stemness factors of Sox2, Oct4, and NANOG. The expression of these factors allows for the cells to overcome their need to be attached to the ECM and travel through the blood stream. We have found through analysis that the membrane bound muicin MUC13 interacts with Sox2 increasing cell stemness leading to the development of anoikis resistance in Colorectal Cancer. Cell cycle analysis of Sw620 cells with high endogenous MUC13 expression showed an 80% less cell death when compare to isogenic Sw480 cells after 48 hours. Western blot anaylsis of the time points 0,24,36, and 48 hrs showed an increase in Sox2 expression and MUC13 expression in Sw620 cells during 24 and 36hrs. To further understand this relationship MUC13 knockdown and overexpressing cells lines will be analyzed to see if any there is a change in the Anoikis phenotype of Sw620 and Sw480 cells. This will also be done with Sox2 knockdown and overexpression. We will also test different therapeutic options, specifically a novel non-viral delivery of MUC13 Crispr Cas9 plasmid to see it effect on Anoikis resistances. Citation Format: Kyle Doxtater, Chidi Zacheaus, Fatemeh Keramatnia, Mehdi Chaib, Manish Triparthi, Subhash Chauhan. MUC13 interacts with SOX2 leading to cell stemness and Anoikis resistance in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2647.