Inducible re-epithelialization of cancer cells increases autophagy and DNA damage: implications for breast cancer dormancy
Drago, D.; Giri, S.; Chattaerjee, R.; Simoni Nieves, A.; Abedrabbo, M.; Genna, A.; Uribe Rios, M. L.; Lindzen, M.; Sekar, A.; Gupta, N.; Aharoni, N.; Bhandari, T.; Mayalagu, A.; Schwarzmuller, L.; Tarade, N.; Zhu, R.; Mohan-Raju, H.-R.; Karatekin, F.; Roncato, F.; Eyal-Lubling, Y.; Keidar, T.; Nof, Y.; Belugali Nataraj, N.; Bernshtein, K. S.; Wagner, B.; Ulhas Nair, N.; Sanghvi, N.; Alon, R.; Seger, R.; Pikarsky, E.; Donzelli, S.; Blandino, G.; Wiemann, S.; Lev, S.; Prywes, R.; Barkan, D.; Rueda, O.; Caldas, C.; Ruppin, E.; Shiloh, Y.; Dahlhoff, M.; Yarden, Y.
Show abstract
Epithelial lineage differentiation is pivotal to mammary gland development and it can pause metastasis of breast cancer (BC) by inducing tumor dormancy. To simulate this, we expressed epithelial genes in mesenchymal BC cells. Inducible expression of the epithelial OVOL genes in metastatic BC cells suppressed proliferation and migration. We found that C1ORF116, an OVOLs target, is susceptible to genetic and epigenetic aberrations in BC. It is regulated by steroids and functions as a putative autophagy receptor that inhibits antioxidants like thioredoxin. Accordingly, boosting epithelialization lowered glutathione, elevated reactive oxygen species and increased both DNA oxidation and double strand breaks. Epithelialization also associated with redistribution of NRF2 and an altered interplay among p38, ATM, and the other kinases regulating the DNA damage response. Hence, hormonal regulation of OVOLs and chronic stress might permit epithelial differentiation and retard exit from dormancy, while altering redox homeostasis and permitting DNA damage accumulation, which may awaken dormant tumors.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Targeting the dependence on PIK3C3-mTORC1 signaling in dormancy-prone breast cancer cells blunts metastasis initiation 96%
- Hormonal regulation of Semaphorin 7a in ER+ breast cancer drives therapeutic resistance 96%
- NRF2 translation block by inhibition of cap-dependent initiation sensitizes lymphoma cells to ferroptosis and CAR-T immunotherapy 96%
Similar papers in this journal
- Loss of EIF4G2 Mediates Aggressiveness in Distinct Human Endometrial Cancer Subpopulations with Poorer Survival Outcome in Patients 96%
- Isoform-specific functions of Numb in breast cancer progression, metastasis and proteome remodeling. 96%
- Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer 96%