Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer Lett. 2018 Dec 1;438:10-16. doi: 10.1016/j.canlet.2018.09.005. Epub 2018 Sep 11.
Krüppel-like factor 4 (KLF4) is an important transcription factor that is expressed in a variety of tissues and regulates many critical physiologic and cellular processes, including cell proliferation, differentiation, stem cell reprogramming, maintenance of genomic stability, and normal tissue homeostasis. KLF4 has both tumor suppressive and oncogenic functions in gastrointestinal and other cancers. These functions are thought to be context dependent, but how KLF4 exerts these differential functions and the molecular mechanisms behind them remain poorly understood. Recent studies have shown that the KLF4 gene undergoes alternative splicing, and the protein products of certain transcripts antagonize wild-type KLF4 function, suggesting an additional layer of regulation of KLF4 function. Therefore, detailed study of KLF4 alternative splicing may not only provide new insights into the complexity of KLF4 functions but also lead to rational targeting of KLF4 for cancer prevention and therapy.
Krüppel 样因子 4（KLF4）是一种重要的转录因子，在多种组织中表达，调节许多关键的生理和细胞过程，包括细胞增殖、分化、干细胞重编程、基因组稳定性维持和正常组织内稳态。KLF4 在胃肠道和其他癌症中具有肿瘤抑制和致癌功能。这些功能被认为是依赖于背景的，但 KLF4 如何发挥这些差异功能以及背后的分子机制仍知之甚少。最近的研究表明，KLF4 基因发生可变剪接，某些转录本的蛋白产物拮抗野生型 KLF4 功能，提示 KLF4 功能的调节有一个额外的层次。因此，对 KLF4 可变剪接的详细研究不仅可以为 KLF4 功能的复杂性提供新的见解，而且可以为 KLF4 的癌症预防和治疗提供合理的靶向。
