NDLI: Targeting SRC Kinase Signaling in Pancreatic Cancer Stem Cells

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Targeting SRC Kinase Signaling in Pancreatic Cancer Stem Cells

Content Provider	MDPI
Author	Sonia, Alcalá Laura, Ruiz-Cañas Juan, Carlos López-Gil Jorge, Martín-Pérez Mayoral-Varo, Víctor Heeschen, Christopher Sainz, Jr. Bruno
Copyright Year	2020
Description	The proto-oncogene nonreceptor tyrosine-protein kinase SRC is a member of the SRC family of tyrosine kinases (SFKs), and its activation and overexpression have been shown to play a protumorigenic role in multiple solid cancers, including pancreatic ductal adenocarcinoma (PDAC). PDAC is currently the seventh-leading cause of cancer-related death worldwide, and, by 2030, it is predicted to become the second-leading cause of cancer-related death in the United States. PDAC is characterized by its high lethality (5-year survival of rate of SRC in PDAC, we set out to determine if SRC kinases are important for PaCSC biology using pharmacological inhibitors of SRC kinases (dasatinib or PP2). Treatment of primary PDAC cultures established from patient-derived xenografts with dasatinib or PP2 reduced the clonogenic, self-renewal, and tumor-initiating capacity of PaCSCs, which we attribute to the downregulation of key signaling factors such as p-FAK, p-ERK1-2, and p-AKT. Therefore, this study not only validates that SRC kinases are relevant and biologically important for PaCSCs but also suggests that inhibitors of SRC kinases may represent a possible future treatment option for PDAC patients, although further studies are still needed.
Starting Page	7437
e-ISSN	14220067
DOI	10.3390/ijms21207437
Journal	International Journal of Molecular Sciences
Issue Number	20
Volume Number	21
Language	English
Publisher	MDPI
Publisher Date	2020-10-09
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Cell Tissue Engineering Src Kinases Cancer Stem Cells Pancreatic Ductal Adenocarcinoma Pp2 Dasatinib Patient-derived Xenografts
Content Type	Text
Resource Type	Article

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