PUBLICATION
Simultaneous targeting of AMPK and mTOR is a novel therapeutic strategy against prostate cancer
- Authors
- Zhao, G., Forn-Cuní, G., Scheers, M., Lindenbergh, P.P., Yin, J., van Loosen, Q., Passarini, L., Chen, L., Snaar-Jagalska, B.E.
- ID
- ZDB-PUB-240211-3
- Date
- 2024
- Source
- Cancer letters 587: 216657 (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B.
- Keywords
- AMPK, LAPC9 organoids, Metabolic stress, Prostate cancer metastasis, Zebrafish xenografts, mTOR crosstalk
- MeSH Terms
-
- AMP-Activated Protein Kinases*/metabolism
- Humans
- Male
- Prostatic Neoplasms*/pathology
- Signal Transduction
- TOR Serine-Threonine Kinases/metabolism
- Tumor Microenvironment
- PubMed
- 38336289 Full text @ Cancer Lett.
Citation
Zhao, G., Forn-Cuní, G., Scheers, M., Lindenbergh, P.P., Yin, J., van Loosen, Q., Passarini, L., Chen, L., Snaar-Jagalska, B.E. (2024) Simultaneous targeting of AMPK and mTOR is a novel therapeutic strategy against prostate cancer. Cancer letters. 587:216657.
Abstract
Metastatic colonization by circulating cancer cells is a highly inefficient process. To colonize distant organs, disseminating cancer cells must overcome many obstacles in foreign microenvironments, and only a small fraction of them survives this process. How these disseminating cancer cells cope with stress and initiate metastatic process is not fully understood. In this study, we report that the metastatic onset of prostate cancer cells is associated with the dynamic conversion of metabolism signaling pathways governed by the energy sensors AMPK and mTOR. While in circulation in blood flow, the disseminating cancer cells display decreased mTOR and increased AMPK activities that protect them from stress-induced death. However, after metastatic onset, the mTOR-AMPK activities are reversed, enabling mTOR-dependent tumor growth. Suppression of this dynamic conversion by co-targeting of AMPK and mTOR signaling significantly suppresses prostate cancer cell and tumor organoid growth in vitro and experimental metastasis in vivo, suggesting that this can be a therapeutic approach against metastasizing prostate cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping