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Johns Hopkins University

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Cancer Res., Jul 03 2024, | https://doi.org/10.1158/0008-5472.CAN-23-3082 E-cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer

Geonhui Lee^1,2, Claudia Wong^1,2, Anna Cho^1,2, Junior J. West³, Ashleigh J. Crawford^1,2, Gabriella C. Russ^o1,2, Bishwa Ranjan Si^1,2, Jungwoo Kim⁴, Lauren Hoffner⁵, Cholsoon Jang⁵, Moonjung Jung⁴, Robert D. Leone⁶, Konstantinos Konstantopoulos^1,2,7,8, Andrew J. Ewald^3,7,8, Denis Wirtz^1,2,8, and Sangmoo Jeong^1,2,8*

¹Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

²Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA

³Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

⁴Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

⁵Department of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA

⁶Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Research Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

⁷Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

⁸Department of Oncology, Sidney Kimmel Comprehensive Cancer Research Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

^*Corresponding author : Sangmoo Jeong, Ph.D.

Abstract

The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial-mesenchymal transition (EMT), 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 PHGDH, 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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-05)
연구진국외 연구진
분야 생명과학 > 세포생물학

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