C045 – Cellular senescence, cancer and aging

Objectives

Our group investigates an essential process for human health and disease, cellular senescence. This program allows the cells to defend themselves against multiple attacks, ensuring that the damaged cells cannot continue dividing and promoting the secretion of multiple factors that activate the immune system and promote the remodeling and repair of the affected tissue. Its correct functioning allows tissue homeostasis to be maintained, but its increase and accumulation, for example, during aging, can result in a multitude of pathologies that we know as diseases associated with aging and, among them, cancer.
In addition, antitumor therapy often leaves tumor cells in a senescent state, which limits their effectiveness. We work to identify new antitumor treatments that allow us to eliminate these senescent tumor cells by specifically inducing their death, which will allow us to have more effective treatments.

Lines of research

• Search for new senolytic compounds: We perform mass screening of compounds to find new molecules with specific cytotoxic activity of senescent cells
• Identification of senescence markers in cancer after chemotherapy: We are looking for biomarkers that can inform us of the induced senescence state in cancer patients after chemotherapy
• Study of the molecular processes that lead to the induction of senescence by chemotherapy in tumor cells: We try to understand how senescence occurs after chemotherapy in order to improve the process, derive the response towards death and avoid the mechanisms of resistance to therapy
• Study of the effect of factors secreted by senescent tumor cells: We analyzed the paracrine effect of the induction of senescence in tumor cells to enhance its possible positive effect and avoid the negative consequences

• Antelo-Iglesias L, Picallos-Rabina P, Estévez-Souto V, Da Silva-Álvarez S, Collado M. The role of cellular senescence in tissue repair and regeneration. Mech Ageing Dev. 2021 Sep;198:111528. doi: 10.1016/j.mad.2021.111528. Epub 2021 Jun 25. PMID: 34181964
• Da Silva-Álvarez S, Collado M. The Jekyll and Hyde of Senescence in Cancer: TIMP1 Controls the Switch from Tumor-Controlling to Tumor-Promoting Senescence. Cancer Cell. 2021 Jan 11;39(1):13-15. doi: 10.1016/j.ccell.2020.12.013. Epub 2020 Dec 24. PMID: 33357453
• Da Silva-Álvarez S, Guerra-Varela J, Sobrido-Cameán D, Quelle A, Barreiro-Iglesias A, Sánchez L, Collado M. Developmentally-programmed cellular senescence is conserved and widespread in zebrafish. Aging (Albany NY). 2020 Sep 29;12(18):17895-17901. doi: 10.18632/aging.103968. Online ahead of print. PMID: 32991320. Free PMC article
• Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, Gil J, Hara E, Krizhanovsky V, Jurk D, Maier AB, Narita M, Niedernhofer L, Passos JF, Robbins PD, Schmitt CA, Sedivy J, Vougas K, von Zglinicki T, Zhou D, Serrano M, Demaria M. Cellular Senescence: Defining a Path Forward. Cell. 2019 Oct 31;179(4):813-827. doi: 10.1016/j.cell.2019.10.005. PMID: 31675495
• Da Silva-Álvarez S, Guerra-Varela J, Sobrido-Cameán D, Quelle A, Barreiro-Iglesias A, Sánchez L, Collado M. Cell senescence contributes to tissue regeneration in zebrafish. Aging Cell. 2020 Jan;19(1):e13052. doi: 10.1111/acel.13052. Epub 2019 Oct 31. PMID: 31670873 Free PMC article.
• Da Silva-Álvarez S, Picallos-Rabina P, Antelo-Iglesias L, Triana-Martínez F, Barreiro-Iglesias A, Sánchez L, Collado M. The development of cell senescence. Exp Gerontol. 2019 Dec;128:110742. doi: 10.1016/j.exger.2019.110742. Epub 2019 Oct 21. PMID: 31648013. Review
• Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, Soprano E, Pedrosa P, Ferreirós A, Barradas M, Hernández-González F, Lalinde M, Prats N, Bernadó C, González P, Gómez M, Ikonomopoulou MP, Fernández-Marcos PJ, García-Caballero T, Del Pino P, Arribas J, Vidal A, González-Barcia M, Serrano M, Loza MI, Domínguez E, Collado M. Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun. 2019 Oct 21;10(1):4731. doi: 10.1038/s41467-019-12888-x. PMID: 31636264. Free PMC article
• Ferreirós A, Pedrosa P, Da Silva-Álvarez S, Triana-Martínez F, Vilas JM, Picallos-Rabina P, González P, Gómez M, Li H, García-Caballero T, González-Barcia M, Vidal A, Collado M. Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency. Stem Cell Reports. 2019 May 14;12(5):1099-1112. doi: 10.1016/j.stemcr.2019.04.006. Epub 2019 May 2. PMID: 31056476. Free PMC article.

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