Transforming growth factor beta-induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration

Autor: Justine Leenders, Assia Tiamiou, Andrei Turtoi, Pascal de Tullio, Arnaud Blomme, Vincenzo Castronovo, Gilles Rademaker, Justine Bellier, Brunella Costanza, Olivier Peulen, Akeila Bellahcene, Philippe Delvenne, Elettra Bianchi
Přispěvatelé: Université de Liège, Cancer Research UK Beatson Institute [Glasgow], Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Rok vydání: 2018
Předmět:
Cancer Research
Stromal cell
endocrine system diseases
integrin
extracellular matrix
[SDV]Life Sciences [q-bio]
Chick Embryo
Focal adhesion
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Cell Movement
Pancreatic cancer
Cell Line
Tumor
medicine
Gene silencing
Animals
Humans
Receptors
Vitronectin
pancreas
Gene Silencing
Extracellular Matrix Proteins
biology
Chemistry
Transforming growth factor beta
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
Survival Analysis
eye diseases
digestive system diseases
3. Good health
Pancreatic Neoplasms
Oncology
030220 oncology & carcinogenesis
Focal Adhesion Protein-Tyrosine Kinases
Cancer research
biology.protein
Signal transduction
Glycolysis
TGFBI
Transforming growth factor
Carcinoma
Pancreatic Ductal
Signal Transduction
Subcellular Fractions
Zdroj: International Journal of Cancer
International Journal of Cancer, Wiley, 2019, 145 (6), pp.1570-1584. ⟨10.1002/ijc.32247⟩
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.32247⟩
Popis: International audience; Pancreatic ductal adenocarcinoma (PDAC) remains a deadly malignancy with no efficient therapy available up-to-date. Glycolysis is the main provider of energetic substrates to sustain cancer dissemination of PDAC. Accordingly, altering the glycolytic pathway is foreseen as a sound approach to trigger pancreatic cancer regression. Here, we show for the first time that high transforming growth factor beta-induced (TGFBI) expression in PDAC patients is associated with a poor outcome. We demonstrate that, although usually secreted by stromal cells, PDAC cells synthesize and secrete TGFBI in quantity correlated with their migratory capacity. Mechanistically, we show that TGFBI activates focal adhesion kinase signaling pathway through its binding to integrin αVβ5, leading to a significant enhancement of glycolysis and to the acquisition of an invasive phenotype. Finally, we show that TGFBI silencing significantly inhibits PDAC tumor development in a chick chorioallantoic membrane assay model. Our study highlights TGFBI as an oncogenic extracellular matrix interacting protein that bears the potential to serve as a target for new anti-PDAC therapeutic strategies.
Databáze: OpenAIRE
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