Serine synthesis pathway upregulated by E-cadherin is essential for the proliferation and metastasis of breast cancers
Abstract 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 thede novoserine 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..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
bioRxiv.org - (2024) vom: 28. März Zur Gesamtaufnahme - year:2024 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Lee, Geonhui [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2023.05.24.541452 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI039692574 |
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520 | |a Abstract 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 thede novoserine 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. | ||
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700 | 1 | |a Wong, Claudia |4 aut | |
700 | 1 | |a Cho, Anna |4 aut | |
700 | 1 | |a West, Junior J. |4 aut | |
700 | 1 | |a Crawford, Ashleigh J. |4 aut | |
700 | 1 | |a Russo, Gabriella C. |4 aut | |
700 | 1 | |a Si, Bishwa Ranjan |4 aut | |
700 | 1 | |a Kim, Jungwoo |4 aut | |
700 | 1 | |a Hoffner, Lauren |4 aut | |
700 | 1 | |a Jang, Cholsoon |4 aut | |
700 | 1 | |a Jung, Moonjung |4 aut | |
700 | 1 | |a Leone, Robert D. |4 aut | |
700 | 1 | |a Konstantopoulos, Konstantinos |4 aut | |
700 | 1 | |a Ewald, Andrew J. |4 aut | |
700 | 1 | |a Wirtz, Denis |4 aut | |
700 | 1 | |a Jeong, Sangmoo |4 aut | |
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