Role of FGFR2c and Its PKCε Downstream Signaling in the Control of EMT and Autophagy in Pancreatic Ductal Adenocarcinoma Cells
| Autor: | Maria Rosaria Torrisi, Francesca Belleudi, Danilo Ranieri, Luisa Guttieri, Salvatore Raffa |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
autophagy
PKCε Cancer Research Cell Autophagy Neoplasms. Tumors. Oncology. Including cancer and carcinogens PDAC Context (language use) Biology medicine.disease_cause behavioral disciplines and activities epithelial–mesenchymal transition (EMT) FGFR2c medicine.anatomical_structure Oncology Downregulation and upregulation medicine Cancer research Carcinogenesis Protein kinase B Transcription factor RC254-282 Intracellular |
| Zdroj: | Cancers, Vol 13, Iss 4993, p 4993 (2021) Cancers Volume 13 Issue 19 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13194993 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is a treatment-resistant malignancy characterized by a high malignant phenotype including acquired EMT signature and deregulated autophagy. Since we have previously described that the aberrant expression of the mesenchymal FGFR2c and the triggering of the downstream PKCε signaling are involved in epidermal carcinogenesis, the aim of this work has been to assess the contribution of these oncogenic events also in the pancreatic context. Biochemical, molecular and immunofluorescence approaches showed that FGFR2c expression impacts on PDAC cell responsiveness to FGF2 in terms of intracellular signaling activation, upregulation of EMT-related transcription factors and modulation of epithelial and mesenchymal markers compatible with the pathological EMT. Moreover, shut-off via specific protein depletion of PKCε signaling, activated by high expression of FGFR2c resulted in a reversion of EMT profile, as well as in a recovery of the autophagic process. The detailed biochemical analysis of the intracellular signaling indicated that PKCε, bypassing AKT and directly converging on ERK1/2, could be a signaling molecule downstream FGFR2c whose inhibition could be considered as possible effective therapeutic approach in counteracting aggressive phenotype in cancer. |
| Databáze: | OpenAIRE |
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