|STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer|
|Wu, Fan1,2; Gao, Pin1; Wu, Wei1; Wang, Zaozao1; Yang, Jie1; Di, Jiabo1; Jiang, Beihai1; Su, Xiangqian1|
|通讯作者||Jiang, Beihai(1) ; Su, Xiangqian(1)|
|关键词||STK25 GOLPH3 Colorectal cancer (CRC) Glycolysis mTOR|
|刊名||JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH|
|WOS标题词||Science & Technology|
|关键词[WOS]||PROTEIN-KINASE STK25 ; UP-REGULATION ; RAPAMYCIN SENSITIVITY ; SIGNALING PATHWAY ; MAMMALIAN TARGET ; SKELETAL-MUSCLE ; GASTRIC-CANCER ; TUMOR-GROWTH ; MTOR ; METABOLISM|
Background: Serine/threonine protein kinase 25 (STK25) is critical in regulating whole-body glucose and insulin homeostasis and the accumulation of ectopic lipids. The Warburg effect, also known as aerobic glycolysis, is an essential metabolic characteristic of cancer cells. However, the effects of STK25 on aerobic glycolysis of cancer cells remain unexplored. The aim of this study is to investigate the role of STK25 in colorectal cancer (CRC) and to elucidate the underlying mechanisms.
Methods: The influences of STK25 on the cell proliferation were evaluated by MTT and colony formation assays. The roles of STK25 in aerobic glycolysis were determined by glucose uptake and lactate production assays. The interaction between STK25 and GOLPH3 was detected by co-immunoprecipitation, GST pull-down, and His-tag pull-down assays. Western blot was used to measure the expression of glycolytic genes, and the status of kinases in mTOR pathway. Moreover, a xenograft mouse model was used to investigate the effects of STK25 in vivo. The prognostic significance of STK25 was analyzed using public CRC datasets by a log-rank test.
Results: STK25 suppressed proliferation, glycolysis and glycolytic gene expression in CRC cells. STK25 interacted with GOLPH3 and mediated glycolysis through GOLPH3-regulated mTOR signaling. Consistent with these observations, silencing of STK25 promoted tumor growth and glycolytic gene expression in an in vivo xenograft mouse model. Moreover, high levels of STK25 correlated with favorable prognosis in patients with CRC.
Conclusions: Our results demonstrated that STK25 negatively regulates the proliferation and glycolysis via GOLPH3-dependent mTOR signaling. Accordingly, STK25 could be a potential therapeutic target for the treatment of CRC.
|通讯作者邮箱firstname.lastname@example.org ; email@example.com|
|作者单位||1.Inner Mongolia Peoples Hosp, Hohhot 010010, Peoples R China;|
2.Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ,Dept Gastrointestinal Surg 4, 52 Fucheng Rd, Beijing 100142, Peoples R China
|Wu, Fan,Gao, Pin,Wu, Wei,et al. STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2018,37.|
|APA||Wu, Fan.,Gao, Pin.,Wu, Wei.,Wang, Zaozao.,Yang, Jie.,...&Su, Xiangqian.(2018).STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,37.|
|MLA||Wu, Fan,et al."STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 37(2018).|