دورية أكاديمية
أعرض في EDS

Targeting SRC Kinase Signaling in Pancreatic Cancer Stem Cells.

التفاصيل البيبلوغرافية
العنوان: Targeting SRC Kinase Signaling in Pancreatic Cancer Stem Cells.
المؤلفون: Alcalá S; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.; Chronic Diseases and Cancer, Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Mayoral-Varo V; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain., Ruiz-Cañas L; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.; Chronic Diseases and Cancer, Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., López-Gil JC; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.; Chronic Diseases and Cancer, Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Heeschen C; Stem Cells & Cancer Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.; Present address: Center for Single-Cell Omics and Key Laboratory of Oncogenes and Related Genes, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China., Martín-Pérez J; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain., Sainz B Jr; Department of Cancer Biology, Instituto de Investigaciones Biomédicas 'Alberto Sols' (IIBM), CSIC-UAM, 28029 Madrid, Spain.; Department of Biochemistry, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain.; Chronic Diseases and Cancer, Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2020 Oct 09; Vol. 21 (20). Date of Electronic Publication: 2020 Oct 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: PubMed not MEDLINE; MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مستخلص: 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 <10%), invasiveness, and chemoresistance, all of which have been shown to be due to the presence of pancreatic cancer stem cells (PaCSCs) within the tumor. Due to the demonstrated overexpression 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.
التعليقات: Erratum in: Int J Mol Sci. 2020 Dec 03;21(23):. (PMID: 33287468)
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معلومات مُعتمدة: RYC-2012-12104 Ministerio de Ciencia, Innovación y Universidades; n/a Fero Foundation; GC16173694BARB Fundación Científica Asociación Española Contra el Cáncer; PI18/00757 Instituto de Salud Carlos III; SAF2016-75991-R Ministerio de Ciencia, Innovación y Universidades
فهرسة مساهمة: Keywords: PP2; SRC kinases; cancer stem cells; dasatinib; pancreatic ductal adenocarcinoma; patient-derived xenografts
تواريخ الأحداث: Date Created: 20201014 Date Completed: 20210226 Latest Revision: 20210226
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7588004
DOI: 10.3390/ijms21207437
PMID: 33050159
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms21207437