| Literature DB >> 27821486 |
Agnieszka A Rucki1,2,3, Kelly Foley1,2,3, Pingbo Zhang4, Qian Xiao1,2, Jennifer Kleponis1,2, Annie A Wu1,2, Rajni Sharma5, Guanglan Mo1,2,6, Angen Liu1, Jennifer Van Eyk7, Elizabeth M Jaffee1,2,3,5,6,8, Lei Zheng9,2,3,6,8.
Abstract
Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the prometastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth, and metastasis. Taken together, our results illuminate tumor-stromal interactions, which drive metastasis, and provide a mechanism-based rationale for a stroma-directed therapy for PDAC. Cancer Res; 77(1); 41-52. ©2016 AACR. ©2016 American Association for Cancer Research.Entities:
Mesh：
Year: 2016 PMID： 27821486 PMCID： PMC5245778 DOI： 10.1158/0008-5472.CAN-16-1383
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701