Gene Regulation, Stems Cells and Cancer

Mechanisms of Cancer and Aging

Group Structure

Bill Keyes
Mari Carmen Ortells (CRG)
Valeria Di Giacomo (“la Caixa” / CRG), Matteo Pecoraro (Plan Nacional / FPI / CRG), Birgit Ritschka (“la Caixa”), Mekayla Storer (“la Caixa”)
Alba Mas (CRG)


Tumour development is a complex process that can be predisposed by a number of criteria. Central to the initiation of tumour growth is the acquisition by a damaged cell of the ability to overcome tumour suppressive mechanisms. Cellular senescence is one such tumour suppressive mechanism, whose inactivation can favour tumour development. Interestingly, the accumulation of senescent cells is also suggested as a cause for aging, supporting the notion that aging results partly as a consequence of tumour suppression.

Another important factor in the development of tumours is the cell type in which the mutations occur. Indeed, it is thought that some cell types might be more susceptible to tumour initiation. In particular, it is thought that endogenous tissue stem cells, by virtue of their hallmark properties including long lifespan, ability to tolerate DNA damage and stress, and their multipotency, are the cells in which tumour initiation is more likely to form. Indeed, for many tumour types, evidence suggests that endogenous stem cells represent the true cell-of-origin in cancer.

However, the predominant variable in the development of cancer is the age of the patient. Cancer is a disease of aging, with the majority of tumours developing later in life. This suggests that there are unknown changes developing in senescent and aged cells, particularly the tissue stem cells that might protect, or yet predispose to tumour development. We hypothesize that by studying the processes of senescence, tumour initiation and stem cell aging, we can unravel new and more relevant molecular pathways that lie at the heart of tumour initiation and maintenance.

Research Projects

  • Investigating the role of p63 and aberrant stem cell proliferation in the pathogenesis of Squamous Cell Carcinoma.
  • Determining the function of p63 in prostate stem cells and prostate tumour development.
  • Exploring the role of cellular senescence in cancer, aging and development.
  • Determining how epidermal stem cells change during normal aging, and the relationship to cancer formation.

Selected Publications

  1. Keyes WM.
    Rearranging senescence: transposable elements become active in aging cells (Comment on DOI 10.1002/bies.201300097).
    Bioessays, 35(12):1023 (2013).
  2. Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, Yosef R, Pilpel N, Krizhanovsky V, Sharpe J, Keyes WM.
    Senescence is a developmental mechanism that contributes to embryonic growth and patterning.
    Cell, 155(5):1119-30 (2013).
  3. Simboeck E, Gutierrez A, Cozzuto L, Beringer M, Caizzi L, Keyes WM, Di Croce L.
    DPY30 regulates pathways in cellular senescence through ID protein expression.
    EMBO J, 32(16):2217-30 (2013).
  4. Mulero MC, Ferres-Marco D, Islam A, Margalef P, Pecoraro M, Toll A, Drechsel N, Charneco C, Davis S, Bellora N, Gallardo F, López-Arribillaga E, Asensio-Juan E, Rodilla V, González J, Iglesias M, Shih V, Mar Albà M, Di Croce L, Hoffmann A, Miyamoto S, Villà-Freixa J, López-Bigas N, Keyes WM, Domínguez M, Bigas A, Espinosa L.
    Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer.
    Cancer Cell, 24(2):151-66 (2013).
  5. Ribeiro JD, Morey L, Mas A, Gutierrez A, Luis NM, Mejetta S, Richly H, Benitah SA, Keyes WM, Di Croce L.
    ZRF1 controls oncogene-induced senescence through the INK4-ARF locus.
    Oncogene, 32(17):2161-8 (2013).
  6. Doles J, Keyes WM.
    Epidermal stem cells undergo age-associated changes.
    Aging (Albany NY), 5(1):1-2 (2013).