Dlx-2 is implicated in TGF-beta- and Wnt-induced epithelial-mesenchymal, glycolytic switch, and mitochondrial repression by Snail activation

作者：Lee Su Yeon; Jeon Hyun Min; Ju Min Kyung; Jeong Eui Kyong; Kim Cho Hee; Yoo Mi Ae; Park Hye Gyeong; Han Song Iy; Kang Ho Sung^*

来源：International Journal of Oncology, 2015, 46(4): 1768-1780.

DOI：10.3892/ijo.2015.2874

• Dlx-2
• Snail
• epithelial-mesenchymal transition
• glycolytic switch
• COXVIc

Epithelial-mesenchymal transition (EMT) and oncogenic metabolism (including glycolytic switch) are important for tumor development and progression. Here, we show that Dlx-2, one of distal-less (Dlx) homeobox genes, induces EMT and glycolytic switch by activation of Snail. In addition, it was induced by TGF-beta and Wnt and regulates TGF-beta- and Wnt-induced EMT and glycolytic switch by activating Snail. We also found that TGF-beta/Wnt suppressed cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, in a Dlx-2/Snail-dependent manner. TGF-beta/Wnt appeared to downregulate the expression of various COX subunits including COXVIc, COXVIIa and COXVIIc; among these COX subunits, COXVIc was a common target of TGF-beta, Wnt, Dlx-2 and Snail, indicating that COXVIc downregulation plays an important role(s) in TGF-beta/Wnt-induced COX inhibition. Taken together, our results showed that Dlx-2 is involved in TGF-beta- and Wnt-induced EMT, glycolytic switch, and mitochondrial repression by Snail activation.

• 出版日期2015-4