Purpose: Homeodomain-interacting protein kinase-2 (HIPK2), a corepressor for homeodomain transcription factors, is a multifunctional kinase whose role in tumor cell survival is not completely clarified. We addressed whether HIPK2 restrains colon tumorigenesis by turning off cytosolic phospholipase A2 (cPLA2)-dependent prostaglandin E2 (PGE2) generation in the light of overwhelming evidence suggesting the contribution of this prostanoid in a variety of cancers.
Experimental Design: In the human colorectal cancer cell line, RKO, we studied the effect of RNA interference for HIPK2 (HIPK2i) on prostanoid biosynthesis, both in the absence and in the presence of the cPLA2 inhibitor arachidonyl trifluoromethyl ketone.
The alpha 6 beta 4 integrin is the receptor for various laminin isoforms and is a component of the hemidesmosome. Increased expression levels of this integrin correlate with the aggressive phenotype of many epithelial tumors compared with surrounding normal tissue. Furthermore, the long cytoplasmic tail of the beta 4 integrin subunit has been implicated in several signal transduction pathways that are involved not only in invasion, but also in proliferation and apoptosis.
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