Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma cells induces chondrosarcoma tumor growth in vivo. TOMM20 drives proliferation, resistance to apoptosis and chemotherapy resistance. Also, TOMM20 induces markers of epithelial to mesenchymal transition (EMT) and metabolic reprogramming in these mesenchymal tumors. In conclusion, TOMM20 drives chondrosarcoma aggressiveness and resistance to chemotherapy.

软骨肉瘤是第二常见的原发性骨恶性肿瘤，占所有原发性骨肉瘤的四分之一。它通常对放射和化学疗法有抵抗力。然而，导致软骨肉瘤癌症侵袭性的分子机制仍不清楚。在这里，我们研究了线粒体转运蛋白在包括化疗耐药性在内的软骨肉瘤侵袭性中的作用。组织学分级和分期是软骨肉瘤最重要的预后生物标志物。我们发现，与低级别肿瘤相比，高级别人类软骨肉瘤具有更高的线粒体蛋白表达，即线粒体外膜复合物亚基 20 (TOMM20) 的转位酶。TOMM20在人软骨肉瘤细胞中的过表达诱导软骨肉瘤肿瘤生长体内。TOMM20 驱动增殖、细胞凋亡抗性和化疗抗性。此外，TOMM20 在这些间充质肿瘤中诱导上皮间质转化 (EMT) 和代谢重编程的标志物。总之，TOMM20 驱动软骨肉瘤的侵袭性和对化疗的抵抗力。