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Inhibition of cell invasion and migration by CEACAM1-4S in breast cancer
Changcheng Yang1, Manlin Cao2, Yiwen Liu1
1Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Abstract:
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cell-cell adhesion molecule, has been revealed to perform an important role in tumor progression. Although there are a number of studies on CEACAM1 in patients with breast cancer, there is limited information on the roles of CEACAM1 in breast cancer metastasis. The present study aimed to identify whether CEACAM1 is involved in breast cancer development and to investigate the underlying mechanisms. First, the expression of CEACAM1 was observed in patients with breast cancer, and the association between CEACAM1 expression levels and migration and invasion of breast cancer cells was analyzed. As there are 12 isoforms of CEACAM1, of which CEACAM1-4S dominates in the human breast epithelium, subsequent study focused on CEACAM1-4S as a representative of all the isoforms. Results of the present study demonstrated that CEACAM1-4S suppresses breast cancer cell invasion and migration in a manner that is dependent on the balance between matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2 and E-/N-cadherin expression. In addition, CEACAM1-4S was likely to cause reversal of epithelial-mesenchymal transition of breast cancer cells through repressing Smad2 and signal transducer and phosphorylation of activator of transcription 3. In conclusion, the present study demonstrated that CEACAM1-4S performs an inhibitory role in breast cancer metastasis, and restoring CEACAM1-4S expression may provide a novel strategy for therapy of patients with metastatic breast cancer.
Insights
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-4S inhibits breast cancer metastasis by suppressing cell invasion and migration. Restoring CEACAM1-4S expression may offer a new therapeutic strategy for metastatic breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is implicated in tumor progression.
- Limited data exists on CEACAM1's role in breast cancer metastasis.
Purpose of the Study:
- To investigate CEACAM1's involvement in breast cancer development and metastasis.
- To elucidate the underlying molecular mechanisms.
Main Methods:
- Assessed CEACAM1 expression in breast cancer patients.
- Analyzed the association between CEACAM1 levels and cancer cell migration/invasion.
- Focused on the CEACAM1-4S isoform.
Main Results:
- CEACAM1-4S significantly suppresses breast cancer cell invasion and migration.
- This suppression is linked to the balance of matrix metalloproteinase 2/tissue inhibitor of metalloproteinase 2 and E-/N-cadherin.
- CEACAM1-4S reverses epithelial-mesenchymal transition by inhibiting Smad2 and STAT3 phosphorylation.
Conclusions:
- CEACAM1-4S plays an inhibitory role in breast cancer metastasis.
- Restoring CEACAM1-4S expression presents a potential therapeutic strategy for metastatic breast cancer.
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