Gene Regulation, Stems Cells and Cancer

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Mechanisms of Cancer and Aging



GROUP LEADER:
Bill Keyes
POSTDOCTORAL RESEARCHER:
Mari Carmen Ortells (CRG / Juan de la Cierva)
PhD STUDENTS:
Valeria Di Giacomo (CRG), Matteo Pecoraro (FPI / CRG), Birgit Ritschka (“la Caixa”), Mekayla Storer (“la Caixa” / CRG)
TECHNICIANS:
Alba Mas (CRG)

Summary

Tumor development is a complex process that can be predisposed by a number of criteria. Central to the initiation of tumor growth is the acquisition by a damaged cell of the ability to overcome tumor suppressive mechanisms. Cellular senescence is one such tumor suppressive mechanism, whose inactivation can favor tumor 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 tumor suppression.

Another important factor in the development of tumors is the cell type in which the mutations occur. Indeed, it is thought that some cell types might be more susceptible to tumor 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 tumor initiation is more likely to form. Indeed, for many tumor 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 tumors 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 tumor development. We hypothesize that by studying the processes of senescence, tumor initiation and stem cell aging, we can unravel new and more relevant molecular pathways that lie at the heart of tumor 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

Storer M and Keyes WM.
“Developing senescence to remodel the embryo.”
Communicative & Integrative Biology, 7(5):1-4 (2014).

Ortells MC and Keyes WM.
“New insights into skin stem cell aging and cancer.”
Biochem Soc. Trans., 42(3):663-9 (2014).