PD-L1 positively regulates MET phosphorylation through inhibiting PTP1B.
PD-L1 positively regulates MET phosphorylation through inhibiting PTP1B.
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DOI：
10.1111/cas.14844
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发表时间：
2021-05
期刊：
影响因子：
5.7
通讯作者：
Hu H
中科院分区：
文献类型：
--
作者：
Lu S;Sun Z;Hu W;Yin S;Zhao C;Hu H
越来越多的证据支持肿瘤内在作用参与PD-L1介导的癌症进展。然而，PD-L1潜在的肿瘤内在功能的机制还不是很清楚。在本研究中，我们发现在肺癌和黑色素瘤细胞系中，PD-L1的表达与MET的磷酸化呈正相关。在体外和体内，抑制PD-L1导致MET磷酸化降低，而用干扰素-γ诱导PD-L1导致依赖PD-L1的MET磷酸化增加。结果表明，PD-L1可以正向调节MET的磷酸化。此外，我们还发现PTP1B参与了PD-L1对MET磷酸化的调节。与PD-L1诱导MET磷酸化一致，抑制PD-L1导致已知的MET下游激酶ERKs的磷酸化减少，并抑制细胞增殖。综上所述，本研究首次证明了作为PD-L1下游的MET通路有助于其肿瘤的内在效应，并为PD-L1的肿瘤内在功能提供了一种新的机制解释，并为免疫治疗和MET靶向治疗在癌症治疗中的结合提供了理论基础。PD-L1的表达与MET的磷酸化水平呈正相关。PD-L1在体外和体内均能正向调节MET的磷酸化。PTP1B是PD-L1调节MET磷酸化的介质。
Increasing bodies of evidence support the involvement of tumor‐intrinsic action in PD‐L1‐mediated cancer progression. However, the mechanisms underlying the tumor‐intrinsic function of PD‐L1 are less well understood. In the present study, we found a positive correlation between PD‐L1 expression and MET phosphorylation in lung cancer and melanoma cell lines. PD‐L1 inhibition led to a decrease in MET phosphorylation, while PD‐L1 induction by IFN‐γ resulted in a PD‐L1‐dependent increase of MET phosphorylation both in vitro and in vivo. The results indicated that MET phosphorylation can be positively regulated by PD‐L1. Furthermore, we identified PTP1B as a mediator contributing to the regulation of MET phosphorylation by PD‐L1. In agreement with the induction of MET phosphorylation by PD‐L1, inhibition of PD‐L1 caused reduced phosphorylation of ERKs, a known downstream kinase of MET, and inhibited cell proliferation. Collectively, the present study demonstrated for the first time that the MET pathway, as a downstream of PD‐L1, contributed to its tumor‐intrinsic effect, and provided a novel mechanistic explanation for the tumor‐intrinsic function of PD‐L1 and a rationale for the combination of immunotherapy and MET‐targeted therapy in cancer treatment. PD‐L1 expression is positively correlated with the levels of MET phosphorylation. MET phosphorylation can be positively regulated by PD‐L1 both in vitro and in vivo. PTP1B is a mediator of the regulation of MET phosphorylation by PD‐L1.
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影响因子：
5.6
作者：
Lu, Shangyun;Zuo, Tao;Tang, Qing-juan
通讯作者：
Tang, Qing-juan
DOI：
10.1158/1541-7786.mcr-16-0350
发表时间：
2017-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kasikara C;Kumar S;Kimani S;Tsou WI;Geng K;Davra V;Sriram G;Devoe C;Nguyen KN;Antes A;Krantz A;Rymarczyk G;Wilczynski A;Empig C;Freimark B;Gray M;Schlunegger K;Hutchins J;Kotenko SV;Birge RB
通讯作者：
Birge RB
影响因子：
7.3
作者：
Morgillo F;Della Corte CM;Fasano M;Ciardiello F
通讯作者：
Ciardiello F
MET 抑制剂通过稳定 PDL1 促进肝脏肿瘤逃避免疫反应
影响因子：
29.4
作者：
Li, Hui;Li, Chia-Wei;Hung, Mien-Chie
通讯作者：
Hung, Mien-Chie
外泌体 PD-L1 有助于免疫抑制并与抗 PD-1 反应相关
影响因子：
64.8
作者：
Chen G;Huang AC;Zhang W;Zhang G;Wu M;Xu W;Yu Z;Yang J;Wang B;Sun H;Xia H;Man Q;Zhong W;Antelo LF;Wu B;Xiong X;Liu X;Guan L;Li T;Liu S;Yang R;Lu Y;Dong L;McGettigan S;Somasundaram R;Radhakrishnan R;Mills G;Lu Y;Kim J;Chen YH;Dong H;Zhao Y;Karakousis GC;Mitchell TC;Schuchter LM;Herlyn M;Wherry EJ;Xu X;Guo W
通讯作者：
Guo W