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Implication of energy sensing pathways in prostate cancer biology

Objective

Prostate cancer is among the most prevalent forms of cancer in men and the fifth cause of dead from cancer in men worldwide. Therefore, the understanding of prostate cancer biology is a key step in the development of new effective therapeutic approaches. In this line, the use of genetically engineered mouse models has been critical in the understanding of the genetic cues that regulate the process of prostate epithelial cell transformation. We have previously characterized the tumor suppressive function of the tumor suppressor PTEN in different stages of prostate cancer, from precancerous lesions to invasive cancer and metastasis. Importantly, we have shown that early and acute loss of PTEN elicits senescence response that functions as a brake for the progression of prostate cancer. Notably, prostate cancer has been demonstrated to be exquisitely sensitive to metabolic changes and to cancer genes altering metabolic homeostasis. In this proposal we aim to ascertain the role of energy sensing pathways in prostate cancer progression, with special emphasis in the crosstalk between the master energy-sensing kinase LKB1 and the tumor suppressor PTEN. Using genetically modified mice and cells, as well as pharmacological agents, we will study i) the contribution of LKB1-loss to the biological features elicited by loss of PTEN, especially the activation of the cellular senescence response, ii) the role of LKB1 signaling in the development of invasive lesions and the onset of metastasis, and iii) the therapeutic relevance of the crosstalk between PTEN and LKB1 in the prostate epithelium. In turn, this proposal aims to contribute to the development of more accurate mouse models of prostate cancer progression as well as to the discovery of potential therapeutic approaches directed to modulate LKB1 signaling in prostate cancer.

Field of science

  • /medical and health sciences/clinical medicine/cancer/prostate cancer

Call for proposal

FP7-PEOPLE-2010-RG
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS
Address
Parque Tecnologico Edificio 801 A
48160 Derio Vizcaya
Spain
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
Alfonso Egaña (Mr.)