Negative correlation between acetyl-CoA acyltransferase 2 and cetuximab resistance in colorectal cancer  

作　　者：Yitao Yuan Xun Sun Mengling Liu Suyao Li Yu Dong Keshu Hu Jiayu Zhang Bei Xu Sining Ma Hesheng Jiang Pengcong Hou Yufu Lin Lu Gan Tianshu Liu 

机构地区：[1]Department of Medical Oncology,Zhongshan Hospital,Fudan University,Shanghai 200032,China [2]Department of Obstetrics and Gynecology,Zhongshan Hospital,Shanghai 200032,China [3]Department of Surgery,Southwest Healthcare,Southern California Medical Education Consortium,Temecula Valley Hospital,Temecula,USA [4]Shanghai Institute of Precision Medicine,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China [5]Department of Oncology,Zhongshan Hospital(Xiamen),Fudan University,Xiamen 361004,China [6]Fudan Zhangjiang Institute,Shanghai 200032,China [7]Center of Evidence Based Medicine,Fudan University,Shanghai 200032,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第9期1467-1478,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81802370 and 8217111492);the Special Clinical Research Program of Shanghai Municipal Health Commission Health Industry(No.202040222);the Xiamen Natural Science Foundation Project(No.3502Z20227111);the Shanghai Natural Science Foundation(No.23ZR1421300).

摘　　要：The emergence of anti-EGFR therapy has revolutionized the treatment of colorectal cancer(CRC).However,not all patients respond consistently well.Therefore,it is imperative to conduct further research to identify the molecular mechanisms underlying the development of cetuximab resistance in CRC.In this study,we find that the expressions of many metabolism-related genes are downregulated in cetuximab-resistant CRC cells compared to their sensitive counterparts.Specifically,acetyl-CoA acyltransferase 2(ACAA2),a key enzyme in fatty acid metabolism,is downregulated during the development of cetuximab resistance.Silencing of ACAA2 promotes proliferation and increases cetuximab tolerance in CRC cells,while overexpression of ACAA2 exerts the opposite effect.RTK-Kras signaling might contribute to the downregulation of ACAA2 expression in CRC,and ACAA2 predicts CRC prognosis in patients with Kras mutations.Collectively,our data suggest that modulating ACAA2 expression contributes to secondary cetuximab resistance in Kras wild-type CRC patients.ACAA2 expression is related to Kras mutation and demonstrates a prognostic role in CRC patients with Kras mutation.Thus,ACAA2 is a potential target in CRC with Kras mutation.

关 键 词：colorectal cancer cetuximab resistance ACAA2 Kras mutation 

分 类 号：R73[医药卫生—肿瘤]