EXPRESSION AND FUNCTION OF APKC KINASE IN COLON CANCER

Shaina Hasan , Anthony S. Perry, Adam Watson, Sourav Ghosh and Diana J. Uribe

EXPRESSION AND FUNCTION OF APKC KINASE IN COLON CANCER

Colorectal cancer is the third leading cause of cancer death in both men and women in the United States. According to the American Cancer Society, 141,210 new cases and 49,380 deaths from colon cancer occurred in 2011 alone. A comprehensive understanding of the molecular mechanisms that are involved in colon cancer progression can facilitate the discovery of novel biomarkers and therapeutic targets. Tumors that arise from epithelial tissues have a distinct hallmark where the once differentiated cells lose their apical-basal cell polarity. This loss of polarity in tumor cells leads to morphological changes in cell architecture, thereby making the tumor cells more mesenchymal. Loss of polarity is often characterized by the loss of cell-cell junctions, dysregulated proliferation and increased cell motility. Our studies of atypical protein kinase C (aPKC), a kinase involved in establishing cell polarity, have determined that this kinase is overexpressed in colon cancer cell lines. Silencing aPKC or the inhibition of aPKC kinase activity with a small molecule ATP-competitive inhibitor reduced cancer cell proliferation. Finally, we have obtained preliminary data that aPKC overexpression and mislocalization is observed in colon cancers. Our results suggest that aPKC may have an important role in the progression of epithelial tumors.

Funding:

National Institute of Health R01 CA149258

Supported in part by funding from the UA Provost's Office

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