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E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.
- Source :
-
Cancer research [Cancer Res] 2024 Sep 04; Vol. 84 (17), pp. 2820-2835. - Publication Year :
- 2024
-
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.<br /> (©2024 American Association for Cancer Research.)
- Subjects :
- Female
Humans
Animals
Mice
Cell Proliferation
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Phosphoglycerate Dehydrogenase metabolism
Phosphoglycerate Dehydrogenase genetics
Neoplasm Metastasis
Antigens, CD metabolism
Cell Movement
Oxidative Stress
Mice, Nude
Serine metabolism
Cadherins metabolism
Breast Neoplasms pathology
Breast Neoplasms metabolism
Breast Neoplasms genetics
Disease Progression
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 84
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 38959339
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-23-3082