Altered surface expression and increased turnover of the α6β4 integrin in an undifferentiated carcinoma
The integrin α6β4, predominantly expressed on tissues of epithelial origin, is known to be variably expressed on carcinomas. The biochemical changes resulting in altered expression during tumor progression are unknown. We have analyzed the expression of α6β4 in a multi-step mouse model of skin carcinogenesis representing normal keratinocyte, benign papilloma and malignant undifferentiated carcinoma. All cell lines expressed the α6 integrin exclusively as the α6β4 integrin heterodimer. Analysis of this integrin by flow cytometry and immunoprecipitation of surface labeled proteins revealed that the undifferentiated carcinoma cells have an ~ 75% reduction in surface expression of the integrin as compared with the keratinocyte and papilloma cell lines. The α6β4 integrin which remains expressed on the carcinoma cells is diffusely distributed in the membrane and has an ~ 2.5-fold increased biological turnover as compared with normal keratinocytes. The decreased biological half-life and the loss of polarized expression of α6β4 on the carcinoma cells suggests an altered functional role for the α6β4 integrin on carcinoma cells during tumor progression. These factors may contribute to the known supression of hemidesmosome structures and the increased migration phenotype associated with some epithelial carcinomas.
Witkowski, Colette M., G. Tim Bowden, Ray B. Nagle, and Anne E. Cress. "Altered surface expression and increased turnover of the α6β4 integrin in an undifferentiated carcinoma." Carcinogenesis 21, no. 2 (2000): 325-330.