Downregulation of Drp1, a fission regulator, is associated with human lung and colon cancers

Abstract

Dynamin-related protein 1 (Drp1), a dynamin-related GTPase, is a key regulator of mitochondrial fission. Although recent studies have shown that Drp1 plays important roles in various important cellular processes, such as maintaining proper mitochondrial function, apoptosis and necrosis, the potential involvement of Drp1 in cancer development has not been fully addressed. To explore the role of Drp1 in cancer, we examined Drp1 levels in various human cancer tissues. Tissue array analysis showed that the level of Drp1 was decreased significantly in malignant colon and lung cancer tissues, whereas no change in Drp1 was observed in breast and prostate tumors. Pairwise comparisons of cancer tissue and adjacent normal tissue from colon and lung cancer patients further confirmed decreases in Drp1 expression of 75% in colon cancer patients and 78% in lung cancer patients. Moreover, Drp1 levels were decreased further with advanced grade in both colon and lung cancers, suggesting that loss of Drp1 is associated with the progression of human lung and colon cancer. Consistent with this observation, knockdown of Drp1 increased cellular migration activity in human lung cancer cells and tumor formation in a xenograft tumor model. Taken together, these results suggest that the loss of Drp1 expression could contribute to the development of human lung and colon cancers.

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