Wang Wanqing, Liu Xue, Zhao Lingling, Jiang Kaipeng, Yu Ziyi, Yang Ruihan, Zhou Wenshuo, Cui Jiuwei, Liang Tingting
Cancer Center, The First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2024 Dec 18;15:1505027. doi: 10.3389/fphar.2024.1505027. eCollection 2024.
F-box and WD repeat domain-containing 7 (FBXW7), formerly known as hCdc4, hAGO Fbw7, or SEL10, plays a specific recognition function in SCF-type E3 ubiquitin ligases. FBXW7 is a well-established cancer suppressor gene that specifically controls proteasomal degradation and destruction of many key oncogenic substrates. The FBXW7 gene is frequently abnormal in human malignancies especially in gastrointestinal cancers. Accumulating evidence reveals that mutations and deletions of FBXW7 are participating in the occurrence, progression and treatment resistance of human gastrointestinal cancers. Considering the current therapeutic challenges faced by gastrointestinal cancers, elucidating the biological function and molecular mechanism of FBXW7 can provide new perspectives and references for future personalized treatment strategies. In this review, we elucidate the key molecular mechanisms by which FBXW7 and its substrates are involved in gastrointestinal cancers. Furthermore, we discuss the consequences of FBXW7 loss or dysfunction in tumor progression and underscore its potential as a prognostic and therapeutic biomarker. Lastly, we propose potential therapeutic strategies targeting FBXW7 to guide the precision treatment of gastrointestinal cancers.
含F盒和WD重复结构域7（FBXW7），以前称为hCdc4、hAGO Fbw7或SEL10，在SCF型E3泛素连接酶中发挥特定识别功能。FBXW7是一种公认的抑癌基因，它特异性地控制许多关键致癌底物的蛋白酶体降解和破坏。FBXW7基因在人类恶性肿瘤中经常出现异常，尤其是在胃肠道癌症中。越来越多的证据表明，FBXW7的突变和缺失参与了人类胃肠道癌症的发生、发展和治疗抵抗。考虑到胃肠道癌症目前面临的治疗挑战，阐明FBXW7的生物学功能和分子机制可为未来的个性化治疗策略提供新的视角和参考。在本综述中，我们阐明了FBXW7及其底物参与胃肠道癌症的关键分子机制。此外，我们讨论了FBXW7缺失或功能障碍在肿瘤进展中的后果，并强调了其作为预后和治疗生物标志物的潜力。最后，我们提出了针对FBXW7的潜在治疗策略，以指导胃肠道癌症的精准治疗。
