Abstract 5744: The role of atypical protein kinase C in colorectal cancer cell growth and proliferation

Abstract

Colorectal cancer (CRC) is the second most common cancer in the world and death from colorectal cancer accounts for 8% of all cancer deaths both in men and women in the United States. CRC is life threatening disease due to therapy resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in colon cancer are still a major challenge for scientists. Hence, investigating the signaling pathways that lead to colon carcinogenesis may give insight into the therapeutic target. In this study, the role of atypical Protein kinase C (aPKC) on colon cancer was identified by using four inhibitors of that particular protein class: 1) ACPD (2-acetyl-1,3-cyclopentanedione and 2) DNDA (3,4-diamino-2,7 naphthalenedisulfonic acid) are non-specific inhibitors of aPKCs; 3) ζ-Stat (8-hydroxy-1, 3, 6-naphthalenetrisulfonic acid) is a specific inhibitor of PKC-ζ; and 4) ICA-I (4, 5-amino-4-carbamoylimidazol-1-yl-2, 3-dihydroxycyclopentyl) methyl dihydrogen phosphate) is a specific inhibitor of PKC-ι. The cell lines tested were HT-29 colon cancer and CCD18CO normal colon epithelial. Although PKC-ι is an oncogene in many cancers, we found that the PKC-ζ was responsible for the abnormal growth and proliferation in HT-29 colon cancer cells. Additionally, the inhibition of aPKCs did not bring any significant toxicity on CCD18CO normal colon cell line. These results suggest the potentiality of utilizing aPKC-ζ inhibitors to block colon cancer cell growth and proliferation. Citation Format: S M Anisul Islam, Mildred Acevedo Duncan. The role of atypical protein kinase C in colorectal cancer cell growth and proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5744. doi:10.1158/1538-7445.AM2017-5744

The modulation of actin dynamics via atypical Protein Kinase-C activated Cofilin regulates metastasis of colorectal cancer cells

“…Previously, our published study showed that the PKC-ζ regulate the growth and proliferation of CRC cells by stimulating Rac1/Pak1/β-Catenin pathway [28,29]. In this study, we evaluated the functional role of atypical PKC in the metastasis of CRC cells.…”

“…Our previous study showed that PKC-ζ regulates the growth of colorectal cancers cells via PKC-ζ/Rac1/Pak1/ β-Catenin pathway [28,29]. Our next target was to examine the role of atypical PKC in another hallmark of cancer, metastasis.…”