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

• Published in: Cancer gene therapy 2023-03, Vol.30 (3), p.404-413
• Main Authors: Lin, Cheng-Han, Lin, Wen-Der, Huang, Yun-Chin, Chen, Yu-Chia, Loh, Zhu-Jun, Ger, Luo-Ping, Lin, Forn-Chia, Li, Hao-Yi, Cheng, Hui-Chuan, Lee, Kuen-Haur, Hsiao, Michael, Lu, Pei-Jung
• Format: Article
• Language: English
• Subjects: 13; 13/105; 13/51; 38/109; 38/39; 59/5; 631/67/1347; 631/67/322; 64/60; 82/51; 96; 96/95; AKT protein; Animals; Biomedical and Life Sciences; Biomedicine; Breast cancer; Carrier Proteins - metabolism; Cell activation; Cell Line, Tumor; DNA microarrays; Female; Gene Expression; Gene Therapy; Humans; Inoculation; Metastases; Metastasis; Mice; Palmitoyl-CoA Hydrolase - metabolism; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Triple Negative Breast Neoplasms - metabolism
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-022-00559-x

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.