title: Elevated expression of TrpC5 and GLUT1 is associated with chemoresistance in colorectal cancer.
abstract: Reprogramming of energy metabolism (aerobic glycolysis) is thought to play an essential role in cancer. Compared to oxidative phosphorylation, aerobic glycolysis consumes more glucose through the upregulation of glucose transporters, notably glucose transporter 1 (GLUT1). Elevated glycolysis occurs in chemoresistant cancer cells, but the detailed mechanism is not well understood. The upregulation of the Ca2+-permeable transient receptor potential channel 5 (TrpC5) activates the Wnt/β-catenin signaling pathway in 5-fluorouracil (5-Fu)-resistant human colorectal cancer (CRC) HCT-8 (HCT-8/5-Fu) cells. In the present study, TrpC5 was overexpressed at the mRNA and protein levels along with GLUT1 in HCT-8/5-Fu cells. Suppression of TrpC5 expression with a TrpC5-specific shRNA reduced the induction of GLUT1 in the HCT-8 cells. The inhibition of the Wnt/β-catenin signaling pathway with XAV939 resulted in a decreased GLUT1 and nuclear c-Myc expression. Further study using clinical specimens validated the positive correlation between TrpC5 and GLUT1 protein levels and showed that a high TrpC5/GLUT1 expression was significantly correlated with chemoresistance. Taken together, we demonstrated the essential role of TrpC5 in GLUT1 induction and revealed that a high TrpC5/GLUT1 expression is associated with chemoresistance in human CRC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Ning
authors.affiliation: Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Ting-Xun
authors.initials: TX
authors.lastname: Lu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D017211:Treatment Failure; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D051272:Glucose Transporter Type 1; D006575:Heterocyclic Compounds, 3-Ring; C495677:SLC2A1 protein, human; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; C544261:XAV939; D005472:Fluorouracil