Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a poor prognosis (5-year survival rate of less than 7%). Its stroma, composed mainly of cancer-associated fibroblasts (CAF), contributes to the aggressiveness of this tumour.
In this study we identify that the Focal adhesion kinase (FAK) protein is a key regulator of the pro-metastatic effect of CAFs, and that its activation is a factor of poor prognosis in PDAC patients. Indeed, the inactivation, genetic or pharmacological, of AKF specifically in CAFs “normalises” the stroma within the primary tumour, remodelling the matrix component and reducing immunosuppressive infiltration. As a result, the invasive potential of the tumour cells and thus the occurrence of spontaneous metastases in vivo are significantly reduced.
This study identifies AKF activity in fibroblasts as a key regulator of PDAC progression and as an independent prognostic marker for patients. Quantifying AKF activity in AFCs would allow the identification of patients at high risk of early relapse and patients likely to benefit from a personalised protocol using AKF inhibitor treatment, molecules currently used in clinical trials.
Discover the published article :
EMBO Mol Med. 2020 Oct 7;e12010.
FAK activity in cancer-associated fibroblasts is a prognostic marker and a druggable key metastatic player in pancreatic cancer
Sonia Zaghdoudi, Emilie Decaup, Ismahane Belhabib, Rémi Samain, Stéphanie Cassant-Sourdy, Julia Rochotte, Alexia Brunel, David Schlaepfer, Jérome Cros, Cindy Neuzillet, Manon Strehaiano, Amandine Alard, Richard Tomasini, Vinothini Rajeeve , Aurélie Perraud, Muriel Mathonnet, Oliver Mt Pearce, Yvan Martineau, Stéphane Pyronnet, Corinne Bousquet, Christine Jean
Key words :
- Pancreatic ductal adenocarcinoma,
- fibroblasts associated with cancer,
- AKF,
- prognostic marker,
- metastases
Contact :
Christine Jean : Equipe 06 Protein synthesis & secretion in carcinogenesis
Mail : christine.jean@inserm.fr
Collaborations :
David Schlaepfer (Department of Reproductive Medicine Moores Cancer Center, University of California San Diego, La Jolla, CA, USA)
Oliver MT Pearce (Centre for Tumour Microenvironment, Barts Cancer Institute, London, UK) Jérome Cros (Department of Pathology, Beaujon Hospital, INSERM U1149, Clichy, France)
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