期刊
BIOMEDICINES
卷 10, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10071652
关键词
Fibroblast Growth Factor Receptor 2 (FGFR2c); pancreatic ductal adenocarcinoma (PDAC); Protein-Kinase C Epsilon (PKC epsilon); Myeloid Cell Leukemia 1 (MCL-1)
资金
- Ministero dell'Istruzione dell'Universita e della Ricerca (MIUR) [20174TB8KW]
- Sapienza, University of Rome, Italy
FGFR2c and its downstream signaling PKC epsilon play a role in the invasive response and anchorage-independent growth of pancreatic ductal adenocarcinoma cells, as well as cell viability, cell migration/invasion, and actin cytoskeleton reorganization.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy whose main characterizations are Kirsten Rat Sarcoma-activating mutations (KRAS) and a highly aggressive phenotype. Based on our recent findings demonstrating that the highly aberrant expression of the mesenchymal isoform of Fibroblast Growth Factor Receptor 2 (FGFR2c) in PDAC cells activates Protein-Kinase C Epsilon (PKC epsilon), which in turn controls receptor-mediated epithelial to mesenchymal transition (EMT), here we investigated the involvement of these signaling events in the establishment of additional tumorigenic features. Using PDAC cell lines expressing divergent levels of the FGFR2c and stable protein depletion approaches by short hairpin RNA (shRNA), we found that FGFR2c expression and its PKC epsilon downstream signaling are responsible for the invasive response to Fibroblast Growth Factor 2 (FGF2) and for anchorage-independent growth. In addition, in vitro clonogenic assays, coupled with the check of the amount of cleaved Poly Adenosine Diphosphate-Ribose Polymerase 1 (PARP1) by Western blot, highlighted the involvement of both FGFR2c and PKC epsilon in cell viability. Finally, monitoring of Myeloid Cell Leukemia 1 (MCL-1) expression and Sarcoma kinase family (SRC) phosphorylation suggested that the FGFR2c/PKC epsilon axis could control cell migration/invasion possibly via MCL-1/SRC-mediated reorganization of the actin cytoskeleton. Being PKCs RAS-independent substrates, the identification of PKC epsilon as a hub molecule downstream FGFR2c at the crossroad of signaling networks governing the main malignant tumor hallmarks could represent an important advance towards innovative target therapies overcoming RAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据