Metastasis suppressor 1 interacts with protein tyrosine phosphatase receptor-δ to regulate adipogenesis
Metastasis suppressor 1 interacts with protein tyrosine phosphatase receptor-δ to regulate adipogenesis
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DOI：
10.1096/fj.202201322r
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发表时间：
2023-04-01
期刊：
影响因子：
4.8
通讯作者：
Wang，Baoli
中科院分区：
文献类型：
--
作者：
Chen，Meng;Dong，Yuan;Wang，Baoli
脂肪生成是一个精细控制的过程，其功能障碍可能导致代谢紊乱，如肥胖。转移抑制因子1（MTSS 1）在多种类型癌症的肿瘤发生和转移中起作用。迄今为止，尚不清楚MTSS 1是否以及如何在脂肪细胞分化中发挥作用。在目前的研究中，我们发现MTSS 1在已建立的间充质细胞系和原代培养的骨髓基质细胞的成脂分化过程中上调。功能获得和功能丧失实验发现MTSS 1促进了间充质祖细胞向脂肪细胞分化。机制研究表明MTSS 1与酪氨酸激酶Src家族成员FYN和蛋白酪氨酸磷酸酶受体-δ（PTPRD）结合并相互作用。我们证明PTPRD能够诱导脂肪细胞分化。PTPRD的过表达减弱了靶向MTSS 1的siRNA诱导的脂肪形成受损。MTSS 1和PTPRD都通过抑制SFKs在Tyr 530的磷酸化和诱导FYN在Tyr 419的磷酸化来激活SFKs。进一步的研究表明，MTSS 1和PTPRD能够激活FYN。总的来说，我们的研究首次揭示了MTSS 1通过与PTPRD相互作用，从而激活SFKs如FYN酪氨酸激酶，在体外脂肪细胞分化中发挥作用。
Adipogenesis is a finely controlled process and its dysfunction may contribute to metabolic disorders such as obesity. Metastasis suppressor 1 (MTSS1) is a player in tumorigenesis and metastasis of various types of cancers. To date, it is not known whether and how MTSS1 plays a role in adipocyte differentiation. In the current study, we found that MTSS1 was upregulated during adipogenic differentiation of established mesenchymal cell lines and primary cultured bone marrow stromal cells. Gain‐of‐function and loss‐of‐function experiments uncovered that MTSS1 facilitated adipocyte differentiation from mesenchymal progenitor cells. Mechanistic explorations revealed that MTSS1 bound and interacted with FYN, a member of Src family of tyrosine kinases (SFKs), and protein tyrosine phosphatase receptor‐δ (PTPRD). We demonstrated that PTPRD was capable of inducing the differentiation of adipocytes. Overexpression of PTPRD attenuated the impaired adipogenesis induced by the siRNA targeting MTSS1. Both MTSS1 and PTPRD activated SFKs by suppressing the phosphorylation of SFKs at Tyr530 and inducing the phosphorylation of FYN at Tyr419. Further investigation showed that MTSS1 and PTPRD were able to activate FYN. Collectively, our study has for the first time unraveled that MTSS1 plays a role in adipocyte differentiation in vitro through interacting with PTPRD and thereby activating SFKs such as FYN tyrosine kinase.