Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms.
Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms.
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DOI：
10.3390/cancers10070239
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发表时间：
2018-07-23
期刊：
影响因子：
5.2
通讯作者：
Sakaguchi M
中科院分区：
文献类型：
--
作者：
Ruma IMW;Kinoshita R;Tomonobu N;Inoue Y;Kondo E;Yamauchi A;Sato H;Sumardika IW;Chen Y;Yamamoto KI;Murata H;Toyooka S;Nishibori M;Sakaguchi M
Embigin是一种跨膜糖蛋白，属于免疫球蛋白超家族，参与前列腺和乳腺的发育。由于embigin在癌症中的作用仍然难以捉摸，我们研究了它的生物学功能和与细胞外S100 A4在前列腺癌进展中的相互作用。我们通过pull-down分析发现，embigin是S100 A4的一种新受体，S100 A4是重要的癌症微环境之一。细胞外S100 A4与embigin的结合通过抑制AMPK活性、激活NF-κB、MMP 9和mTORC 1信号传导以及抑制自噬（其增加前列腺癌细胞运动性）介导前列腺癌进展。我们还发现，embigin促进前列腺癌的生长，球体和集落形成能力，并独立于S100 A4化疗后的生存。体内生长小鼠模型证实了embigin及其细胞质尾在介导前列腺肿瘤生长中的重要性。此外，embigin和p21 WAF 1可用于预测前列腺癌患者的生存。我们的研究结果首次证实S100 A4-embigin/AMPK/mTORC 1/p21 WAF 1和NF-κB/MMP 9轴是前列腺癌进展的重要致癌分子级联。我们提出，embigin和p21 WAF 1可用作预后生物标志物，抑制S100 A4-embigin结合的策略可能是前列腺癌患者的治疗方法。
Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.
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DOI：
10.1158/1541-7786.mcr-15-0213
发表时间：
2015-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
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Dan HC
影响因子：
64.8
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通讯作者：
Ruggero, Davide
影响因子：
6.4
作者：
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影响因子：
8.8
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影响因子：
4.6
作者：
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通讯作者：
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