Yang Jia-Sin, Chou Chia-Hsuan, Hsieh Yi-Hsien, Tang Chih-Hsin, Lu Ko-Hsiu, Yang Shun-Fa
Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J Cell Mol Med. 2025 Aug;29(15):e70763. doi: 10.1111/jcmm.70763.
Osteosarcoma(OS), the most common primary bone cancer, has high metastatic potential and a high mortality rate. Carbonic anhydrase IX (CAIX), a hypoxia-induced transmembrane protein, is highly expressed in numerous cancers. Over the past decades, scientists have made extensive efforts to determine the role of CAIX in various cancers. However, the effects of CAIX on the metastasis of OS cell lines remain unclear. We examined the effectiveness of CAIX for inducing the invasion and migration of human OS cells and the underlying molecular mechanisms. We established CAIX-overexpressing human OS cells and found markedly increased migratory and invasive abilities in HOS and U2OS cell lines. In addition, CAIX overexpression increased the messenger ribonucleic acid (mRNA) and protein expression levels of heat shock protein family A member 6 (HSPA6) and the phosphorylation of adenosine-monophosphate-activated protein kinase (AMPK) signalling proteins. With HSPA6 knockdown, U2OS cells exhibited significantly reduced migratory and invasive abilities. Moreover, treatment with an AMPK inhibitor (dorsomorphin) suppressed CAIX-induced HSPA6 expression and the metastasis of U2OS cells. In conclusion, the results indicate that CAIX overexpression mediates HSPA6 expression through the AMPK signalling pathway, which consequently induces the metastasis of OS cells.
骨肉瘤（OS）是最常见的原发性骨癌，具有高转移潜能和高死亡率。碳酸酐酶IX（CAIX）是一种缺氧诱导的跨膜蛋白，在多种癌症中高表达。在过去几十年里，科学家们为确定CAIX在各种癌症中的作用付出了巨大努力。然而，CAIX对OS细胞系转移的影响仍不清楚。我们研究了CAIX诱导人OS细胞侵袭和迁移的有效性及其潜在分子机制。我们建立了过表达CAIX的人OS细胞，发现HOS和U2OS细胞系的迁移和侵袭能力显著增强。此外，CAIX过表达增加了热休克蛋白家族A成员6（HSPA6）的信使核糖核酸（mRNA）和蛋白质表达水平以及腺苷单磷酸激活蛋白激酶（AMPK）信号蛋白的磷酸化。敲低HSPA6后，U2OS细胞的迁移和侵袭能力显著降低。此外，用AMPK抑制剂（多柔比星）处理可抑制CAIX诱导的HSPA6表达和U2OS细胞的转移。总之，结果表明CAIX过表达通过AMPK信号通路介导HSPA6表达，从而诱导OS细胞转移。
