E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.
Cancer Res
; 84(17): 2820-2835, 2024 Sep 04.
Article
in En
| MEDLINE
| ID: mdl-38959339
ABSTRACT
The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers. Significance:
E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin-expressing tumors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serine
/
Breast Neoplasms
/
Cadherins
/
Disease Progression
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Res
Year:
2024
Document type:
Article
Country of publication: