Abstract 4931: Yap1 regulates the transcription of cofilin to facilitate the metastatic movement of colorectal cancer cells

Abstract

Abstract Colorectal cancer (CRC) is one of the most leading death-causing cancers in the United States which accounts for 23,380 estimated death cases in 2019 as per American Cancer Society. Surgical removal of cancerous tissue coupled with chemotherapeutic intervention is the primary treatment of metastatic CRC and the only hope of enhanced survival. Dysregulation of kinases is pivotal in the various pathological process, including cancer. In addition, the metastatic events in a cancer cell are usually brought by the alteration of different key molecules. One such key molecule is called cofilin that acts on the actin cytoskeleton to induce metastatic phenotype in cancerous cells. In this study, we used two atypical Protein Kinase C (PKC) inhibitors, namely ICA-I (a PKC-ι inhibitor) and ζ-Stat (a PKC-ζ inhibitor), to investigate the role of atypical PKCs in regulating the expression of cofilin in metastatic colorectal cells. Our findings suggested that the atypical PKC inhibitors reduced the expression and translocation of Yap1 from cytosol to nucleus which ultimately leads to the reduced expression of cofilin in CRC cells. This mechanistic study provides an important insight into the metastatic behavior of the cancerous colorectal cells that can be used to target metastasis regulating molecules to improve the survival rate in patients with CRC. Citation Format: S M Anisul Islam, Mildred Acevedo-Duncan. Yap1 regulates the transcription of cofilin to facilitate the metastatic movement of colorectal cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4931.