Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer
Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer
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Semaphorin 4C 促进乳腺癌巨噬细胞募集和血管生成
DOI：
10.1158/1541-7786.mcr-18-0933
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发表时间：
2019
影响因子：
5.2
通讯作者：
Gao Qinglei
中科院分区：
文献类型：
--
作者：
Yang Jie;Zeng Zhen;Qiao Long;Jiang Xuefeng;Ma Jingjing;Wang Junnai;Ye Shuangmei;Ma Quanfu;Wei Juncheng;Wu Mingfu;Huang Xiaoyuan;Ma Ding;Gao Qinglei
脑信号蛋白是一个进化上保守的形态发生分子的大家族，与排斥轴突导向相关。有趣的是，最近的研究表明，semaphorins参与癌症的进展。Semaphorin 4C（SEMA 4C）长期以来被认为是神经元迁移基因，但我们检测到它在许多恶性肿瘤中也高度表达。在皮下肿瘤模型的研究中，我们发现SEMA 4C表达促进肿瘤生长和进展。我们发现SEMA 4C参与维持肿瘤细胞的自我更新，可能是通过调节p53通路。抑制内源性SEMA 4C在肿瘤细胞中的表达会损害生长，并诱导衰老和细胞周期停滞在G2期。此外，我们发现SEMA 4C通过以丛蛋白B2依赖的方式激活NF-κB通路诱导肿瘤细胞中血管生成素和集落刺激因子-1（CSF-1）的产生。总之，乳腺癌细胞中的SEMA 4C表达促进癌细胞增殖、巨噬细胞募集和血管生成。因此，抑制SEMA 4C活性可能是人类乳腺癌的一种新的治疗策略。在乳腺癌中，SEMA 4C通路的治疗靶向可能会阻止肿瘤生长，血管生成，转移和进展。
Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many malignant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell-cycle arrest in the G2-phase. In addition, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexinB2-dependent manner. In conclusion, SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. Thus, inhibition of SEMA4C activity may be a novel therapeutic strategy for human breast cancer. Implications: In breast cancer, therapeutic targeting of the SEMA4C pathway may prevent tumor growth, angiogenesis, metastasis, and progression.