磷酸化或乙酰化修饰使Fascin的促癌功能翻转  

Phosphorylation or Acetylation Alters the Oncogenic Role of Fascin

作　　者：李大嘉 许丽艳 程银伟 李恩民 LI Da-Jia;XU Li-Yan;CHENG Yin-Wei;LI En-Min(The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area,Department of Biochemistry and Molecular Biology,Shantou University Medical College,Shantou 515041,Guangdong,China;Institute of Oncologic Pathology,Shantou University Medical College,Shantou 515041,Guangdong,China;Cancer Research Center,Shantou University Medical College,Shantou 515041,Guangdong,China;The Laboratory for Cancer Molecular Biology,Shantou Academy Medical Sciences,Shantou 515041,Guangdong,China)

机构地区：[1]汕头大学医学院生物化学与分子生物学教研室,潮汕沿海地区高发肿瘤分子生物学广东省高校重点实验室,广东汕头515041 [2]汕头大学医学院肿瘤病理研究室,广东汕头515041 [3]汕头大学医学院肿瘤研究中心,广东汕头515041 [4]汕头市医学科学院肿瘤分子生物学研究室,广东汕头515041

出　　处：《中国生物化学与分子生物学报》2024年第5期674-684,共11页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81872372,No.82273108,No.82173034;No.81902469);广东省教育创新团队资助项目(No.2021KCXTD005);2020年李嘉诚基金跨学科研究资助重点项目(No.2020LKSFG07B)。

摘　　要：大量研究结果表明,食管鳞癌等恶性肿瘤中,Fascin异常高表达并发挥促癌功能,其与癌症患者的不良预后密切相关。近年来,包括本实验室在内,多家实验室的研究结果一致表明,磷酸化或乙酰化修饰可使Fascin的促癌功能翻转,犹如川剧中的“变脸”。最近,本室进一步研究发现,Fascin的翻译后修饰明显影响Fascin小分子抑制剂的抑癌效果,提示以Fascin为靶点的抗肿瘤药物研究应该将Fascin翻译后修饰状态纳入是否适合用药的评价体系中。为此,本文在系统评述Fascin促癌功能的基础上,重点讨论了翻译后修饰对Fascin功能的调控作用,以及翻译后修饰对Fascin小分子抑制剂抑癌功效的影响;同时还对相关领域针对Fascin的未来研究趋势进行了展望。Fascin displays elevated expression in malignant tumors,such as esophageal squamous cell carcinoma,and exerts a pro-cancer effect that is closely associated with poor prognosis among cancer patients.In recent years,our research,along with that of others,has consistently demonstrated that phosphorylation or acetylation modifications can effectively reverse the oncogenic function of Fascin,just like the“face-changing”in Sichuan Opera.Recently,we have further revealed that post-translational modifications of Fascin affect the anticancer efficacy of small-molecule Fascin inhibitors.This finding suggests that therapeutics targeting Fascin should incorporate the status of post-translational modifications of Fascin into the drug efficacy evaluation framework.Here,we present a review on the oncogenic function of Fascin,focusing on discussing the effect of post-translational modifications on the function of Fascin and the efficacy of small-molecule Fascin inhibitors,and provide insights into future research directions in the field of Fascin.

关 键 词：FASCIN 蛋白质翻译后修饰 肿瘤 微丝成束蛋白抑制剂 

分 类 号：Q245[生物学—细胞生物学]