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

Abstract

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.

• Authors: Cheng-Han Lin, Wen-Der Lin, Yun-Chin Huang, Yu-Chia Chen, Zhu-Jun Loh, Luo-Ping Ger, Forn-Chia Lin, Hao-Yi Li, Hui-Chuan Cheng, Kuen-Haur Lee, Michael Hsiao, Pei-Jung Lu
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 30 Issue 3 Pg. 404-413 (03 2023) ISSN: 1476-5500 [Electronic] England
• PMID: 36400965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Carrier Proteins
• CTMP protein, mouse
• Palmitoyl-CoA Hydrolase
• Proto-Oncogene Proteins c-akt
• THEM4 protein, human

Topics

• Animals
• Humans
• Mice
• Carrier Proteins (metabolism)
• Cell Line, Tumor
• Palmitoyl-CoA Hydrolase (metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Triple Negative Breast Neoplasms (metabolism)
• Female