Abstract 5155: The modulation of actin dynamics via atypical protein kinase-C activated cofilin regulates migration of colorectal cancer cells

Abstract

Abstract Colorectal cancer (CRC) is the second most common cancer in both men and women in the United States. The exact mechanism of CRC cells migration is poorly understood. Actin polymerization is thought to be an initial step in cancer cells motility cycle which drives the formation of cell protrusions that defines the direction of migration and initiate cell crawling. Cofilin is a significant actin regulating molecule that can regulate the migration of cancer cells by the formation of lamellipodia and filopodia. In this study, the effect of atypical Protein Kinase C (aPKC) on cofilin in CRC was studied by using two inhibitors of aPKC: 1) ICA-I (5-amino-1-(2,3-dihydroxy-4-hydroxymethyl) cyclopentyl)-1H-imidazole-4-carboxamide) is a specific inhibitor of PKC-ι and 2) ζ-Stat (8-hydroxy-1, 3, 6-naphthalenetrisulfonic acid) is a specific inhibitor of PKC-ζ. The cell lines tested were CCD18CO normal colon fibroblast and LOVO & RKO metastatic CRC cells. The inhibition of aPKC did not bring any significant toxicity in CCD18CO colon fibroblasts cells. However, our data showed that the inhibition of aPKC blocks the migration of CRC cells migration by increasing the level of cofilin phosphorylation at serine-3. Additionally, the aPKCs inhibition brought a significant reduction of CRC cells proliferation along with the reduction of survival markers. Our findings suggest that the PKC-ι and/or PKC-ζ may be responsible for the migration of CRC cells as well as carcinogenesis. These results suggest the possibility of utilizing aPKCs as the potential therapeutic targets for the CRC cells metastasis. Citation Format: S M Anisul Islam, Khandker Mohammad Khalid, Raja Reddy Bommareddy, Rekha Patel, Mildred Acevedo-Duncan. The modulation of actin dynamics via atypical protein kinase-C activated cofilin regulates migration of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5155.