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SRPX 和 HMCN1 调节癌相关成纤维细胞促进卵巢癌的侵袭。

SRPX and HMCN1 regulate cancer‑associated fibroblasts to promote the invasiveness of ovarian carcinoma.

机构信息

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, R.O.C.

出版信息

Oncol Rep. 2019 Dec;42(6):2706-2715. doi: 10.3892/or.2019.7379. Epub 2019 Oct 17.

Abstract

Cancer‑associated fibroblasts (CAFs) are known to be essential in cancer initiation and development. However, the role of CAFs in promoting ovarian cancer (OC) invasion remains to be fully elucidated. To address this in the present study, 49 clinical OC specimens were used to evaluate the roles of CAFs in promoting ovarian tumor migration and invasion and disease progression. It was found that the sushi repeat‑containing protein, X‑linked (SRPX) and hemicentin 1 (HMCN1) genes were significantly upregulated in CAFs from high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) samples, the two major histological types of OC with frequently poor patient survival rates. The short hairpin (sh)RNA‑mediated silencing of SRPX and HMCN1 in fibroblasts significantly suppressed the Transwell invasive activities of OC cells. Further experiments showed that SRPX and HMCN1 regulated the invasiveness of OC via the Ras homology family member A (RhoA) signaling pathway in fibroblasts. Therefore, the findings of the present study suggest that targeting the CAF genes, SRPX and HMCN1, can inhibit OC migration and invasion. These data highlight the importance of CAF‑OC crosstalk signaling in cancer invasion and demonstrate the potential for improved efficacy of OC treatment by targeting CAF‑SRPX/HMCN1.

摘要

癌症相关成纤维细胞(CAFs)在癌症的发生和发展中起着至关重要的作用。然而,CAFs 在促进卵巢癌(OC)侵袭中的作用仍有待充分阐明。为了解决这一问题,本研究使用了 49 份临床 OC 标本,评估了 CAFs 在促进卵巢肿瘤迁移和侵袭以及疾病进展中的作用。研究发现,富含 sushi 重复的 X 连锁蛋白(SRPX)和半钙蛋白 1(HMCN1)基因在高级别浆液性癌(HGSC)和透明细胞癌(CCC)样本中的 CAFs 中显著上调,这两种组织学类型是 OC 的主要类型,患者的生存率往往较低。短发夹 RNA(shRNA)介导的 SRPX 和 HMCN1 在成纤维细胞中的沉默显著抑制了 OC 细胞的 Transwell 侵袭活性。进一步的实验表明,SRPX 和 HMCN1 通过成纤维细胞中的 Ras 同源家族成员 A(RhoA)信号通路调节 OC 的侵袭性。因此,本研究的结果表明,靶向 CAF 基因 SRPX 和 HMCN1 可以抑制 OC 的迁移和侵袭。这些数据强调了 CAF-OC 串扰信号在癌症侵袭中的重要性,并表明通过靶向 CAF-SRPX/HMCN1 提高 OC 治疗效果的潜力。

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