Department of Biology, Jackson State University, 1400 Lynch Street, Box 18540, Jackson, MS 39217, USA.
Research Centers in Minority Institutions Center for Environmental Health (RCMI-CEH), Jackson State University, 1400 Lynch Street, Box 18540, Jackson, MS 39217, USA.
Int J Environ Res Public Health. 2018 Jul 9;15(7):1442. doi: 10.3390/ijerph15071442.
Basal cell carcinoma (BCC) is the most frequently occurring form of all cancers. The cost of care for BCC is one of the highest for all cancers in the Medicare population in the United States. Activation of Hedgehog (Hh) signaling pathway appears to be a key driver of BCC development. Studies involving mouse models have provided evidence that activation of the glioma-associated oncogene (GLI) family of transcription factors is a key step in the initiation of the tumorigenic program leading to BCC. Activation of the Wnt pathway is also observed in BCCs. In addition, the Wnt signaling pathway has been shown to be required in Hh pathway-driven development of BCC in a mouse model. Cross-talks between Wnt and Hh pathways have been observed at different levels, yet the mechanisms of these cross-talks are not fully understood. In this review, we examine the mechanism of cross-talk between Wnt and Hh signaling in BCC development and its potential relevance for treatment. Recent studies have identified insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a direct target of the Wnt/β-catenin signaling, as the factor that binds to GLI1 mRNA and upregulates its levels and activities. This mode of regulation of GLI1 appears important in BCC tumorigenesis and could be explored in the treatment of BCCs.
基底细胞癌（BCC）是所有癌症中最常见的一种。在美国医疗保险人群中，BCC 的治疗费用是所有癌症中最高的之一。Hedgehog（Hh）信号通路的激活似乎是 BCC 发展的关键驱动因素。涉及小鼠模型的研究提供了证据，表明Glioma-associated oncogene（GLI）转录因子家族的激活是导致 BCC 的肿瘤发生程序启动的关键步骤。Wnt 途径的激活也在 BCC 中观察到。此外，在小鼠模型中，已经表明 Wnt 信号通路在 Hh 通路驱动的 BCC 发育中是必需的。Wnt 和 Hh 途径之间的串扰在不同水平上已经被观察到，然而这些串扰的机制尚未完全理解。在这篇综述中，我们研究了 Wnt 和 Hh 信号在 BCC 发展中的串扰机制及其在治疗中的潜在相关性。最近的研究已经确定胰岛素样生长因子 2 mRNA 结合蛋白 1（IGF2BP1），Wnt/β-catenin 信号的直接靶标，作为与 GLI1 mRNA 结合并上调其水平和活性的因子。这种调节 GLI1 的模式在 BCC 肿瘤发生中似乎很重要，并且可以在 BCC 的治疗中进行探索。
