MACC1 decreases the chemosensitivity of gastric cancer cells to oxaliplatin by regulating FASN expression.
The effect of chemotherapeutic agents is limited as a result of drug resistance, which demands prompt solutions provided by clinical studies. To date, the underlying mechanisms of chemotherapy resistance are relatively unknown. Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and prognosis of gastric cancer (GC). Bioinformatic analysis revealed that MACC1 is positively associated with fatty acid synthase (FASN), a major enzyme of lipogenesis, and drives chemoresistance to oxaliplatin in GC. Similar findings were demonstrated in two GC cell lines (BGC-823 and MKN-28) with MACC1 ectopic expression. We next employed FASN inhibitor C75 or siFASN (small interfering RNA targeted to FASN) to block endogenous fatty acid metabolism and it was revealed that cell proliferation and chemoresistance to oxaliplatin induced by MACC1 upregulation were attenuated by FASN blockade to various extents. Conclusively, these outcomes highlight a novel role of MACC1 in GC cell lipogenesis, and suggest that MACC1 may be an attractive target to decrease oxaliplatin resistance in GC.
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Jiangman
J
Duan
Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Lishan
L
Chen
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Minyu
M
Zhou
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Jingwen
J
Zhang
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Li
L
Sun
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Na
N
Huang
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Jianping
J
Bin
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Yulin
Y
Liao
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.
Wangjun
W
Liao
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; C544162:MACC1 protein, human; D009944:Organoplatinum Compounds; D015534:Trans-Activators; D014157:Transcription Factors; D000077150:Oxaliplatin; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I