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Role of stromal fibroblasts in prostate carcinoma progression and metabolic reprogramming of cancer cells

Marini, Alberto (2014) Role of stromal fibroblasts in prostate carcinoma progression and metabolic reprogramming of cancer cells. Doctoral Thesis.

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Cancer-Associated Fibroblasts (CAFs) play a key role in cancer malignancy, eliciting a pro-oxidant environment and endowing cancer cells with invasive motility, stem cell properties, metastatic spread and deeply metabolic alterations. Our aim is to understand the interplay among CAFs, oxidative stress and metabolic reprogramming of prostate cancer (PCa) cells during tumor progression, as well as their possible involvement in drug resistance. We demonstrated a reciprocal metabolic reprogramming of CAFs and PCa cells. In particular, CAFs shift their metabolism towards a more glycolytic one, through a HIF1- and oxidative stress-dependent extrusion of lactate. This catabolite shuttles back to cancer cells, which use it for TCA cycle and protein synthesis, fueling cancer cell proliferation. Furthermore, metabolically reprogrammed CAFs express carbonic anhydrase IX, which is mandatory to elicit the secretion of metalloprotease-2 and -9 through acidification of extracellular milieu, thus driving epithelial-mesenchymal transition in PCa cells. We finally reported the importance of metabolic adaptations during chemoresistance acquisition. Indeed, docetaxel-resistant PCa cells undergo an escape from glycolytic metabolism with a potential involvement of mitochondrial respiration to confer a metabolic advantage to these cells.

Item Type:Doctoral Thesis
ID Code:9461
Contributors:Pintus, Gianfranco and Chiarugi, Paola
Publisher:Università degli studi di Sassari
Uncontrolled Keywords:Cancer, metabolic, reprogramming, prostate, fibroblasts
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Cicli, scuole e corsi:Ciclo 26 > Scienze biomolecolari e Biotecnologiche > Biochimica e Biologia molecolare
Deposited On:01 Apr 2014 10:47

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