Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea; Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, South Korea.
Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, South Korea.
Biochem Biophys Res Commun. 2019 Sep 3;516(4):1110-1115. doi: 10.1016/j.bbrc.2019.07.011. Epub 2019 Jul 6.
Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a role in terminal differentiation of epidermal keratinocytes. There are conflicting reports regarding the role of KLF4 in tumor development, with both the tumor suppressive and/or oncogenic properties depending on different conditions and cell types. In this study, we investigated the functional importance of KLF4 in cutaneous squamous cell carcinoma (SCC). Immunohistochemistry showed that KLF4 expression was relatively low in SCC lesion compared to normal epidermis. To examine the effects of KFL4, we transduced SCC lines (SCC12 and SCC13 cells) with the KLF4-expressing recombinant adenovirus. Overexpression of KLF4 significantly decreased cell proliferation and colony forming activity. In addition, overexpression of KLF4 markedly reduced invasive potential, along with the downregulation of epithelial-mesenchymal transition (EMT)-related molecules. In a mechanistic study, KLF4 inhibited SOX2, of which expression is critical for tumor initiation and growth of SCC. Further investigations indicated that SOX2 expression is induced by TGF-β/SMAD signaling, and that overexpression of KLF4 inhibited SMAD signaling via upregulation of SMAD7, an important inhibitory SMAD molecule. Based on these data, KLF4 plays a tumor suppressive role in cutaneous SCC cells.
Kruppel 样因子 4（KLF4）是一种锌指转录因子，在表皮角质形成细胞的终末分化中发挥作用。关于 KLF4 在肿瘤发展中的作用存在相互矛盾的报道，其抑瘤和/或致癌特性取决于不同的条件和细胞类型。在这项研究中，我们研究了 KLF4 在皮肤鳞状细胞癌（SCC）中的功能重要性。免疫组织化学显示，与正常表皮相比，SCC 病变中的 KLF4 表达相对较低。为了研究 KFL4 的作用，我们用表达 KLF4 的重组腺病毒转导 SCC 细胞系（SCC12 和 SCC13 细胞）。KLF4 的过表达显著降低了细胞增殖和集落形成活性。此外，KLF4 的过表达显著降低了侵袭潜力，同时下调了上皮-间充质转化（EMT）相关分子。在一项机制研究中，KLF4 抑制了 SOX2 的表达，SOX2 的表达对 SCC 的肿瘤起始和生长至关重要。进一步的研究表明，SOX2 的表达是由 TGF-β/SMAD 信号诱导的，而 KLF4 的过表达通过上调重要的抑制性 SMAD 分子 SMAD7 抑制了 SMAD 信号。基于这些数据，KLF4 在皮肤 SCC 细胞中发挥抑瘤作用。
