| Autor: |
Lee G, Wong C, Cho A, West JJ, Crawford AJ, Russo GC, Si BR, Kim J, Hoffner L, Jang C, Jung M, Leone RD, Konstantopoulos K, Ewald AJ, Wirtz D, Jeong S |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 26. Date of Electronic Publication: 2024 Mar 26. |
| DOI: |
10.1101/2023.05.24.541452 |
| Abstrakt: |
The loss of E-cadherin (E-cad), an epithelial cell adhesion molecule, has been implicated in the epithelial-mesenchymal transition (EMT), promoting invasion and migration of cancer cells and, consequently, metastasis. However, recent studies have demonstrated that E-cad supports the survival and proliferation of metastatic cancer cells, suggesting that our understanding of E-cad in metastasis is far from comprehensive. Here, we report that E-cad upregulates the de novo serine synthesis pathway (SSP) in breast cancer cells. The SSP provides metabolic precursors for biosynthesis and resistance to oxidative stress, critically beneficial for E-cad-positive breast cancer cells to achieve faster tumor growth and more metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered the proliferation of E-cad-positive breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. Our findings reveal that E-cad adhesion molecule significantly reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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