Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, NE, 68198, USA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, NE, 68198, USA; Department of Otolaryngology-Head & Neck Surgery, University of Nebraska Medical Center, NE, 68198, USA; Department of Biotechnology, Central University of Kashmir, Ganderbal, Jammu and Kashmir, India -191201.
Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188362. doi: 10.1016/j.bbcan.2020.188362. Epub 2020 Apr 13.
Trefoil factors 1, 2, and 3 (TFFs) are a family of small secretory molecules involved in the protection and repair of the gastrointestinal tract (GI). TFFs maintain and restore epithelial structural integrity via transducing key signaling pathways for epithelial cell migration, proliferation, and invasion. In recent years, TFFs have emerged as key players in the pathogenesis of multiple diseases, especially cancer. Initially recognized as tumor suppressors, emerging evidence demonstrates their key role in tumor progression and metastasis, extending their actions beyond protection. However, to date, a comprehensive understanding of TFFs' mechanism of action in tumor initiation, progression and metastasis remains obscure. The present review discusses the structural, functional and mechanistic implications of all three TFF family members in tumor progression and metastasis. Also, we have garnered information from studies on their structure and expression status in different organs, along with lessons from their specific knockout in mouse models. In addition, we highlight the emerging potential of using TFFs as a biomarker to stratify tumors for better therapeutic intervention.
三叶因子 1、2 和 3（TFFs）是一组参与胃肠道（GI）保护和修复的小分泌分子。TFF 通过转导上皮细胞迁移、增殖和侵袭的关键信号通路，维持和恢复上皮结构的完整性。近年来，TFFs 已成为多种疾病（尤其是癌症）发病机制中的关键因素。最初被认为是肿瘤抑制因子，新出现的证据表明它们在肿瘤进展和转移中起着关键作用，其作用超出了保护范围。然而，迄今为止，对 TFF 在肿瘤发生、进展和转移中的作用机制仍缺乏全面的了解。本综述讨论了所有三种 TFF 家族成员在肿瘤进展和转移中的结构、功能和机制意义。此外，我们还从不同器官的结构和表达状态以及在小鼠模型中进行特定敲除的研究中获取了信息。此外，我们还强调了将 TFF 用作生物标志物来分层肿瘤以进行更好的治疗干预的新潜力。
