Abnormality of apico-basal polarity in adenocarcinoma.

Apico-basal polarity is a fundamental property of the epithelium that functions as a barrier, holds cells together, and determines the directions of absorption and secretion. Apico-basal polarity is regulated by extracellular matrix-integrin binding and downstream signaling pathways, including focal adhesion kinase, rouse-sarcoma oncogene (SRC), and RHO/RHO-associated kinase (ROCK). Loss of epithelial cell polarity plays a critical role in the progression of cancer cells. However, in differentiated carcinomas, polarity is not completely lost but dysregulated. Recent progress with a three-dimensional culture of primary cancer cells allowed for studies of the mechanism underlying the abnormality of polarity in differentiated cancers, including flexible switching of polarity status in response to the microenvironment. Invasive micropapillary carcinoma (MPC) is one of the histopathological phenotypes of adenocarcinoma, which is characterized by inverted polarity. Aberrant activation of RHO-ROCK signaling plays a critical role in the MPC phenotype. Establishing in vitro models will contribute to future drug targeting of the abnormal polarity status in cancer.