期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 51, 期 1, 页码 169-183出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.4018
关键词
pancreatic cancer; Fyn; integrin; alternative splicing; hnRNPs
类别
资金
- National Natural Science Foundation of China [81430063]
- Natural Science Foundation of Southwest Hospital [SWH2016JCYB-46]
Pancreatic cancer is characterized by a dense desmoplastic reaction in which extracellular matrix proteins accumulate and surround tumor cells. Integrins and their related signaling molecules are associated with progression of pancreatic cancer. In the present study, the association between the metastasis of pancreatic cancer and the expression of hnRNP E1 and integrin beta 1 was evaluated. In vitro and in vivo experiments were designed to study the mechanism underlying the regulation of integrin p1 splicing by the Fyn/hnRNP E1 spliceosome. Expression of hnRNP E1 and integrin beta 1A were associated with metastasis of pancreatic cancer. Inhibition of Fyn activity upregulated the expression of P21-activated kinase 1 and promoted the phosphorylation and nuclear localization of hnRNP E1, leading to the construction of a spliceosome complex that affected the alterative splicing of integrin beta 1. In the hnRNP E1 spliceosome complex, hnRNP A1 and serine/arginine-rich splicing factor 1 were responsible for binding to the pre-mRNA of integrin beta 1. Suppression of Fyn activity and/or overexpression of hnRNP E1 decreased the metastasis of pancreatic cancer cells. In pancreatic cancer, the present study demonstrated a novel mechanism by which Fyn/hnRNP E1 signaling regulates pancreatic cancer metastasis by affecting the alternative splicing of integrin beta 1. hnRNP El and integrin beta 1A are associated with the metastasis of pancreatic cancer and may be novel molecular targets for pancreatic cancer treatment.
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