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LAMA5 通过激活 Notch 信号通路促进卵巢癌细胞增殖和迁移。

LAMA5 promotes cell proliferation and migration in ovarian cancer by activating Notch signaling pathway.

机构信息

Department of Gynecology, First Affiliated Hospital, Shihezi University, Shihezi, China.

The NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University, Shihezi, China.

出版信息

FASEB J. 2023 Sep;37(9):e23109. doi: 10.1096/fj.202300306R.

Abstract

LAMA5 (laminin α5) is a member of the laminin family. Despite the recent research implicating LAMA5 in cancer, the function of LAMA5 has remained uncertain in the progression of ovarian cancer (OC). Here, we investigated the functional influences of LAMA5 knockdown on OC in vitro and in vivo. In this study, we used immunohistochemistry (IHC) analysis to detect the relative expression of LAMA5 in OC and non-cancer tissues, and we analyzed its connection with the overall survival (OS) of OC patients. To prove the role of LAMA5 in cell proliferation, migration, and invasion, LAMA5 expression in OC cell lines was inhibited by lentivirus. Compared with normal fallopian tube tissue, epithelial ovarian cancer (EOC) tissue showed critically higher LAMA5 expression levels; additionally, high LAMA5 levels were a poor predictor of OS. We found that cell progression was restrained in LAMA5-knockdown OC cell lines in vivo and in vitro. Finally, LAMA5 might be a commanding inducer of the expression of epithelial-mesenchymal transition (EMT) and Notch signaling pathway-related markers. Together, our research indicates that LAMA5 is highly connected to OC progression as it may play a role in the EMT process through the Notch signaling pathway.

摘要

层粘连蛋白 5(laminin α5)是层粘连蛋白家族的一员。尽管最近的研究表明 LAMA5 与癌症有关,但 LAMA5 在卵巢癌(OC)进展中的功能仍不确定。在这里,我们研究了 LAMA5 敲低对 OC 的体外和体内功能影响。在这项研究中,我们使用免疫组织化学(IHC)分析来检测 OC 和非癌组织中 LAMA5 的相对表达,并分析其与 OC 患者总生存率(OS)的关系。为了证明 LAMA5 在细胞增殖、迁移和侵袭中的作用,我们通过慢病毒抑制 OC 细胞系中的 LAMA5 表达。与正常输卵管组织相比,上皮性卵巢癌(EOC)组织中 LAMA5 的表达水平显著升高;此外,LAMA5 水平高是 OS 不良的预测指标。我们发现,LAMA5 敲低的 OC 细胞系在体内和体外的细胞进展受到抑制。最后,LAMA5 可能是上皮间质转化(EMT)和 Notch 信号通路相关标志物表达的重要诱导剂。总之,我们的研究表明,LAMA5 与 OC 进展高度相关,因为它可能通过 Notch 信号通路在 EMT 过程中发挥作用。

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