Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong, 510080, China.
Mol Cell Endocrinol. 2019 Jan 15;480:122-132. doi: 10.1016/j.mce.2018.10.021. Epub 2018 Nov 2.
Dermatopontin (DPT), a noncollagenous extracellular matrix component, has been illustrated to regulate cellular proliferation and invasiveness in several types of neoplasms. Nevertheless, the biological functions of DPT in cell proliferation, especially papillary thyroid cancer (PTC) cell proliferation, remain unknown, as do the mechanisms underlying its effects. In this study, we detected low DPT expression in PTC, which was related to higher T classifications. Ectopic DPT expression impeded cell proliferation both in vitro and in vivo. Furthermore, we illustrated that DPT down-regulated MYC, which in turn targeted CDK4, CDK6 and p21, through the ERK pathway. These results suggest that DPT regulates CDK4, CDK6 and p21, through MEK-ERK-MYC signaling to repress PTC proliferation.
真皮桥蛋白（DPT）是一种非胶原细胞外基质成分，已被证明可调节多种类型肿瘤中的细胞增殖和侵袭性。然而，DPT 在细胞增殖中的生物学功能，特别是在甲状腺乳头状癌（PTC）细胞增殖中的生物学功能尚不清楚，其作用的机制也不清楚。在这项研究中，我们检测到 PTC 中 DPT 表达水平较低，与较高的 T 分类有关。异位 DPT 表达抑制了体外和体内的细胞增殖。此外，我们还表明，DPT 通过 ERK 通路下调 MYC，进而靶向 CDK4、CDK6 和 p21。这些结果表明，DPT 通过 MEK-ERK-MYC 信号通路调节 CDK4、CDK6 和 p21，从而抑制 PTC 的增殖。
