High PKC alpha and low E-cadherin expression contribute to high migratory activity of colon carcinoma cells

The protein kinase C (PKC) is a family of serine/threonine kinases that are key regulatory enzymes involved in growth, differentiation, cytoskeletal r eorganization, tumor promotion, and migration. We investigated the function al involvement of PKC isotypes and of E-cadherin in the regulation of the l ocomotion of six human colon-adenocarcinoma cell lines. The different level s of the PKC alpha and the E-cadherin expression have predictable implicati ons in the spontaneous locomotory activity. With the use of PKC alpha -spec ific inhibitors (safingol, Go6976) as well as the PKC delta -specific inhib itor rottlerin, we showed that only PKC alpha plays a major role in the reg ulation of tumor cell migration. The results were verified by knocking out the translation of PKC isozymes with the use of an antisense oligonucleotid e strategy. After stimulation with phorbol ester we observed a translocatio n and a colocalization of the activated PKC alpha at the plasma membrane to the surrounding extracellular matrix. Furthermore, we investigated the fun ctional involvement of E-cadherin in the locomotion with the use of a block ing antibody. A high level of PKC alpha expression together with a low E-ca dherin expression was strongly related to a high migratory activity of the colon carcinoma cells. This correlation was independent of the differentiat ion grade of the tumor cell lines.