LACTB 通过下调 RHOC/Cofilin 信号通路抑制脑胶质瘤的迁移和侵袭。
LACTB suppresses migration and invasion of glioblastoma via downregulating RHOC/Cofilin signaling pathway.
机构信息
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.
Department of Neurosurgery, Southwest Medical University, Lu Zhou, China.
出版信息
Biochem Biophys Res Commun. 2022 Nov 12;629:17-25. doi: 10.1016/j.bbrc.2022.09.002. Epub 2022 Sep 6.
Glioblastoma (GBM) is the most malignant tumor in human brain. High invasiveness of this tumor is the main reason causing treatment failure and recurrence. Previous study has found that LACTB is a novel tumor suppressor in breast cancer. Moreover, the function of LACTB in other tumors and mechanisms involving LACTB were also reported. However, the role and relevant mechanisms of LACTB in GBM invasion remains to be revealed. Our aim is to investigate the role LACTB in GBM migration and invasion. We found that LACTB was downregulated in gliomas compared to normal brain tissues. Overexpression of LACTB suppressed migration and invasion of LN229 and U87 cell lines. Mechanistically, LACTB overexpression downregulated the mesenchymal markers. Moreover, LACTB overexpression downregulated the expression of RHOC and inhibited RHOC/Cofilin signaling pathway. The study suggests that LACTB suppresses migration and invasion of GBM cell lines via downregulating RHOC/Cofilin signaling pathway. These findings suggest that LACTB may be a potential treatment target of GBM.
胶质母细胞瘤（GBM）是人类大脑中最恶性的肿瘤。这种肿瘤的高度侵袭性是导致治疗失败和复发的主要原因。先前的研究发现，LACTB 是乳腺癌中的一种新型肿瘤抑制因子。此外，LACTB 在其他肿瘤中的功能以及涉及 LACTB 的机制也有报道。然而，LACTB 在 GBM 侵袭中的作用和相关机制仍有待揭示。我们的目的是研究 LACTB 在 GBM 迁移和侵袭中的作用。我们发现 LACTB 在神经胶质瘤中相对于正常脑组织表达下调。LACTB 的过表达抑制了 LN229 和 U87 细胞系的迁移和侵袭。在机制上，LACTB 的过表达下调了间充质标志物。此外，LACTB 的过表达下调了 RHOC 的表达并抑制了 RHOC/Cofilin 信号通路。该研究表明，LACTB 通过下调 RHOC/Cofilin 信号通路抑制 GBM 细胞系的迁移和侵袭。这些发现表明，LACTB 可能是 GBM 的潜在治疗靶点。
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