Wang Yizhi, An Yang, Ma Yi, Guo Junchao
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.
Department of Anesthesia, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Lett. 2019 Apr;17(4):3625-3634. doi: 10.3892/ol.2019.10036. Epub 2019 Feb 13.
Cancer is a principal cause of human morbidity and mortality, with gastrointestinal malignancies, in particular, resulting in a marked number of tumor-associated mortalities. The progression of gastrointestinal malignancy is regulated by a variety of aberrantly expressed proteins, a number of which facilitate tumor progression, whereas, others function as tumor suppressors. The detection of such proteins not only contributes to the early diagnosis of cancer, they may additionally serve as potential therapeutic targets. In normal tissues, numerous proteins encoded by proto-oncoproteins are degraded by ubiquitylation enzymes, consisting of F-box/WD-40 repeat-containing protein 7 (Fbw7) and other proteins, thus avoiding tumorigenesis and maintaining homeostasis. In tumor tissues, the downregulation of Fbw7, caused by various factors, leads to disorders in ubiquitinase synthesis, which may induce tumor progression and chemoresistance, particularly in gastrointestinal malignancy. Therefore, an in-depth study of the regulatory mechanisms involved in disorders of Fbw7 expression and the role of Fbw7 in chemoresistance of gastrointestinal tumors may suggest improvements for early diagnostic screening and targeted therapy.
癌症是人类发病和死亡的主要原因,尤其是胃肠道恶性肿瘤,导致大量与肿瘤相关的死亡。胃肠道恶性肿瘤的进展受多种异常表达的蛋白质调控,其中一些促进肿瘤进展,而另一些则起肿瘤抑制作用。检测这些蛋白质不仅有助于癌症的早期诊断,还可能作为潜在的治疗靶点。在正常组织中,原癌蛋白编码的许多蛋白质被泛素化酶降解,这些酶由含F-box/WD-40重复序列的蛋白7(Fbw7)和其他蛋白质组成,从而避免肿瘤发生并维持体内平衡。在肿瘤组织中,各种因素导致的Fbw7下调会导致泛素酶合成紊乱,这可能诱导肿瘤进展和化疗耐药,尤其是在胃肠道恶性肿瘤中。因此,深入研究Fbw7表达紊乱的调控机制以及Fbw7在胃肠道肿瘤化疗耐药中的作用,可能为早期诊断筛查和靶向治疗带来改进。