Year: 2024
Type: article
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.
Source: Cancer Research
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Funders: Breast Cancer Research Foundation, American Association for the Study of Liver Diseases, Maryland Stem Cell Research Fund, METAvivor, Edward Mallinckrodt, Jr. Foundation, Jayne Koskinas Ted Giovanis Foundation for Health and Policy, National Institutes of Health, Sidney Kimmel Comprehensive Cancer Center, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1165598027, G1230067360, G1297238948, G1467304686, G1912770925, G28496096, G2990623361, G3318661017, G4009280720, G4601445628, G5353294268, Targeting Tumor Metabolism as a Means of Enhancing Immunotherapy, G601512365, G6035581646, G6629105355, Novel sources of endogenous DNA damage in hematopoietic stem progenitor cells, G9000009912, G9000018586, G9000041231, G9000069527, G9000205485, G9000233196, G9000279130, Center for 3D Imaging in Cancer Cell Biology, Metabolic regulation of exosome biogenesis
OpenAlex ID: W4400274452