title: LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world, and the development of new therapeutic targets is needed. Recent studies have shown that aerobic glycolysis, also known as the Warburg effect, mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A (LDHA) which executed the final step of aerobic lactate production has been reported to be involved in the tumor progression. However, the function of LDHA in ESCC has not been investigated. In this study, it was found that LDHA was up-regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited cell growth and cell migration in vitro as well as tumorigenesis in vivo. With regard to the molecular mechanism, silencing the expression of LDHA was related to decreased AKT activation and cyclin D1 expression and increased cleavage of PARP and caspase 8. Taken together, our findings suggest that LDHA plays an important role in the progression of ESCC by modulating cell growth, and LDHA might be a potential therapeutic target in ESCC.
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Rd, Shanghai, 200030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Tiejun
authors.initials: T
authors.lastname: Zhao
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhong
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D007527:Isoenzymes; D034741:RNA, Small Interfering; D019938:Cyclin D1; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053181:Caspase 8