MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer.
MIIP functions as a novel ligand for ITGB3 to inhibit angiogenesis and tumorigenesis of triple-negative breast cancer.
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MIIP作为ITGB3的新型配体抑制三阴性乳腺癌的血管生成和肿瘤发生
DOI：
10.1038/s41419-022-05255-0
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发表时间：
2022-09-21
影响因子：
9
通讯作者：
Li, Pu
中科院分区：
文献类型：
--
作者：
Gao, Yujing;Fang, Yujie;Huang, Yongli;Ma, Rui;Chen, Xixi;Wang, Fang;Pei, Xiuying;Gao, Yuanqi;Chen, Xuehua;Liu, Xinrui;Shan, Jingxuan;Li, Pu
迁移和侵袭抑制蛋白（MIIP）已被鉴定为多种癌症类型中的肿瘤抑制因子。虽然MIIP被报道通过抑制癌细胞的增殖和转移来发挥肿瘤抑制功能，但对其详细机制知之甚少。在本研究中，我们发现MIIP是三阴性乳腺癌预后的有利指标。MIIP在体内外均能抑制三阴性乳腺癌细胞的肿瘤血管生成、增殖和转移。从机制上讲，MIIP直接与ITGB 3相互作用并抑制其下游信号传导。结果，由于泛素介导的降解升高，β-连环蛋白减少，导致VEGFA产生和上皮间质转化下调。更重要的是，我们发现RGD基序对于MIIP与ITGB 3结合并执行有效的肿瘤抑制作用是必需的。我们的研究结果揭示了MIIP抑制三阴性乳腺癌肿瘤发生的新机制，因此MIIP是该疾病有前途的分子生物标志物或治疗靶点。
Migration and invasion inhibitory protein (MIIP) has been identified as a tumor suppressor in various cancer types. Although MIIP is reported to exert tumor suppressive functions by repressing proliferation and metastasis of cancer cells, the detailed mechanism is poorly understood. In the present study, we found MIIP is a favorable indicator of prognosis in triple-negative breast cancer. MIIP could inhibit tumor angiogenesis, proliferation, and metastasis of triple-negative breast cancer cells in vivo and in vitro. Mechanistically, MIIP directly interacted with ITGB3 and suppressed its downstream signaling. As a result, β-catenin was reduced due to elevated ubiquitin-mediated degradation, leading to downregulated VEGFA production and epithelial mesenchymal transition. More importantly, we found RGD motif is essential for MIIP binding with ITGB3 and executing efficient tumor-suppressing effect. Our findings unravel a novel mechanism by which MIIP suppresses tumorigenesis in triple-negative breast cancer, and MIIP is thus a promising molecular biomarker or therapeutic target for the disease.
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影响因子：
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