MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling

	MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling
	Shen, QS; Han, YF; Wu, K; He, YM; Jiang, XL; Liu, PS; Xia, CF; Xiong, QX; Liu, R; Chen, QM; Zhang, Y; Zhao, S; Yang, CP; Chen, YB
	2022
发表期刊	SIGNAL TRANSDUCTION AND TARGETED THERAPY
ISSN	2095-9907
卷号	7 期号:1
摘要	The incidence of cutaneous melanoma (CM) has been increasing annually worldwide. In this study, we identify that MrgprF, a MAS related GPR family member, is decreased in cutaneous melanoma tissues and cell lines due to hypermethylation of its promoter region, and show that patients with CM expressing high levels of MrgprF exhibit an improved clinical outcome. We demonstrate that MrgprF forced expression inhibits tumor cell proliferation, migration, xenograft tumor growth, and metastasis. On the contrary, MrgprF knockdown promotes tumor cell proliferation and transformation of immortalized human keratinocyte-HaCaT cells, supporting the inhibitory role of MrgprF during tumor progression. Mechanistic studies reveal that MrgprF reduces the phosphoinositol-3-kinase (PI3K) complex formation between p101 and p110 gamma subunits, the critical step for phosphatidylinositol-(3, 4)-P2 (PIP2) conversion to phosphatidylinositol-(3, 4, 5)-P3 (PIP3), and then reduces the activation of PI3K/Akt signaling. This effect can be reversed by Akt specific agonist SC79. In addition, AMG 706, a previously documented inhibitor for endothelial cell proliferation, is identified as a potential agonist for MrgprF, and can impede tumor growth both in vitro and in vivo. Taken together, our findings suggest that MrgprF, a novel tumor suppressor in cutaneous melanoma, may be useful as a therapeutic target in the future.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13284
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Shen, QS,Han, YF,Wu, K,et al. MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2022,7(1).
APA	Shen, QS.,Han, YF.,Wu, K.,He, YM.,Jiang, XL.,...&Chen, YB.(2022).MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling.SIGNAL TRANSDUCTION AND TARGETED THERAPY,7(1).
MLA	Shen, QS,et al."MrgprF acts as a tumor suppressor in cutaneous melanoma by restraining PI3K/Akt signaling".SIGNAL TRANSDUCTION AND TARGETED THERAPY 7.1(2022).

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