title: Dlx-2 is implicated in TGF-β- and Wnt-induced epithelial-mesenchymal, glycolytic switch, and mitochondrial repression by Snail activation.
abstract: 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-β and Wnt and regulates TGF-β- and Wnt-induced EMT and glycolytic switch by activating Snail. We also found that TGF-β/Wnt suppressed cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, in a Dlx-2/Snail-dependent manner. TGF-β/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-β, Wnt, Dlx-2 and Snail, indicating that COXVIc downregulation plays an important role(s) in TGF-β/Wnt-induced COX inhibition. Taken together, our results showed that Dlx-2 is involved in TGF-β- and Wnt-induced EMT, glycolytic switch, and mitochondrial repression by Snail activation.
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Su Yeon
authors: SY
authors: Lee
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Hyun Min
authors: HM
authors: Jeon
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Min Kyung
authors: MK
authors: Ju
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Eui Kyong
authors: EK
authors: Jeong
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Cho Hee
authors: CH
authors: Kim
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Mi-Ae
authors: MA
authors: Yoo
authors: Nanobiotechnology Center, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Hye Gyeong
authors: HG
authors: Park
authors: The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759, Republic of Korea.
authors: Song Iy
authors: SI
authors: Han
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
authors: Ho Sung
authors: HS
authors: Kang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006019:Glycolysis; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D008928:Mitochondria / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta