Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 1 Miecznikowa St., 02-096 Warsaw, Poland.
Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, VIC 3086, Australia.
Int J Mol Sci. 2020 Nov 22;21(22):8843. doi: 10.3390/ijms21228843.
Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.
Krüppel 样因子 4（KLF4）是一种在进化中高度保守的转录因子。它在诱导多能干细胞方面的作用尤为突出。此外，KLF4 在癌症中也发挥着多种作用。大多数研究的结果表明，KLF4 是一种肿瘤抑制因子。然而，KLF4 的功能受到许多层面的调控。这些调控包括转录调控、可变剪接、miRNA、翻译后修饰、亚细胞定位、蛋白质稳定性以及与其他分子的相互作用。简单的检测转录水平或蛋白质水平的实验无法解决这种复杂性，因此可能会产生误导性的结果。肿瘤亚型也很重要；例如，在前列腺癌中，KLF4 在惰性肿瘤中高表达，抑制肿瘤进展，而在侵袭性前列腺肿瘤中则不存在。KLF4 在调节对许多已知药物的反应方面也很重要，并且在肿瘤微环境中也发挥作用。关于 KLF4 参与癌症的上游调控因子、下游靶标和信号通路的信息越来越多。此外，KLF4 在组织稳态、细胞完整性以及向恶性肿瘤进展的整体调控中发挥着关键作用。在这里，我们总结和分析了关于这个令人着迷的转录因子的最新发现。
