文章：

羧基末端调节蛋白促进三阴性乳腺癌的肿瘤转移

Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer 

原文发布日期：2022-11-18 

英文摘要：

Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway. 

摘要翻译： 

目前，乳腺癌的存活率超过90%，但一旦癌细胞转移至远端器官，存活率便会急剧下降至30%以下。三阴性乳腺癌占所有乳腺癌的15-20%。由于治疗策略有限，相较于非三阴性乳腺癌，三阴性乳腺癌（TNBC）的预后和诊断结果较差。因此，开发针对TNBC转移的靶向治疗仍是亟待解决的问题。本研究发现，高羧基末端调节蛋白（CTMP）与TNBC患者的复发和无病生存率显著相关。过表达CTMP可促进BT549细胞的迁移和侵袭能力，而下调CTMP表达则抑制MDA-MB-231细胞的迁移和侵袭能力。体内接种高CTMP细胞会增强小鼠的远端转移，而注射CTMP下调的MDA-MB-231细胞的小鼠转移发生率降低。基因表达微阵列分析表明，与亲代细胞相比，CTMP过表达细胞中Akt依赖通路显著增强。通过Akt抑制剂处理或共表达显性失活形式的Akt蛋白来阻断Akt激活，可成功消除CTMP介导的TNBC细胞侵袭。我们的研究结果表明，CTMP是TNBC患者复发和不良无病生存率的潜在诊断标志物，且CTMP通过依赖Akt激活的途径促进TNBC转移。

原文链接：

Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer