title: Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis through upregulation of SNAIL expression.
abstract: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in multiple cellular functions including metabolism and gene transcription. Our previous study showed that GAPDH expression was elevated in colon cancer and further upregulated in liver metastatic tissues, suggesting a possilbe role of GAPDH in promoting cancer metastasis. The present study was designed to investigate the underlying mechanism, using multiple experimental approaches including genetic silencing of GAPDH expression by short hairpin RNA (shRNA) and biochemcial/molecular analyses of the key events involved in glycolytic metabolism and epithelial-mesenchymal transition (EMT). We showed that silencing of GAPDH expression resulted in a significant reduction of glycolysis in colon cancer cell lines, accompanied by a decrease in cell proliferation and an apparent change in cell morphology associated with alterations in actin expression and phalloidine staining patterns. Furthermore, GAPDH suppression also caused a downregulation of gene expression involved in cancer stem-like cells and EMT. CHIP assay and co-immunoprecipitation revealed that GAPDH physically interacted with the transcriptional factor Sp1 and enhance the expression of SNAIL, a major regulator of EMT. Suppression of GAPDH expression resulted in a signficant decrease in SNAIL expression, leading to inhibition of EMT and attenuation of colon cancer cell migration in vitro and reduced metastasis in vivo. Overall, the present study suggests that GAPDH plays an important role in cancer metastasis by affecting EMT through regulation of Sp1-mediated SNAIL expression.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Medical Oncology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510700, P.R. China.
authors.forename: Amin
authors.initials: A
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Lu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Wen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases