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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/12777
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| Title: | Inactivation of apc induces cd34 upregulation to promote epithelial-mesenchymal transition and cancer stem cell traits in pancreatic cancer |
| Authors: | Hsieh, MJ;Chiu, TJ;Lin, YC;Weng, CC;Weng, YT;Hsiao, CC;Cheng, KH |
| Contributors: | National Institute of Cancer Research |
| Abstract: | Pancreatic cancer (PC) is a highly lethal malignancy due to the cancer routinely being diagnosed late and having a limited response to chemotherapy. Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic malignant tumor, representing more than 85% of all pancreatic cancers. In the present study, we characterized the phenotypes of concomitant P53 and APC mutations in pancreatic neoplasms driven by the oncogene KRAS in genetically modified mice (GEMM). In this GEMM setting, APC haploinsufficiency coupled with P53 deletion and KRASG12D activation resulted in an earlier appearance of pancreatic intraepithelial neoplasia (PanIN) lesions and progressed rapidly to highly invasive and metastatic PDAC. Through a microarray analysis of murine PDAC cells derived from our APC-deficient PDAC model, we observed that APC loss leads to upregulated CD34 expression in PDAC. CD34 is a member of a family of single-pass transmembrane proteins and is selectively expressed in hematopoietic progenitor cells, vascular endothelial cells, interstitial precursor cells, and various interstitial tumor cells. However, the functional roles of CD34 in pancreatic cancer remain unclear. Thus, in this study, we explored the mechanisms regarding how CD34 promotes the deterioration of pancreatic malignancy. Our results demonstrated that the increased expression of CD34 induced by APC inactivation promotes the invasion and migration of PDAC cells, which may relate to PDAC metastasis in vivo. Collectively, our study provides first-line evidence to delineate the association between CD34 and the APC/Wnt pathway in PDAC, and reveals the potential roles of CD34 in PDAC progression. |
| Date: | 2020-06-20 |
| Relation: | International Journal of Molecular Sciences. 2020 Jun 20;21(12):Article number 4473. |
| Link to: | http://dx.doi.org/10.3390/ijms21124473 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000550166800001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85086906638 |
| Appears in Collections: | [其他] 期刊論文
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| SCP85086906638.pdf | | 1565Kb | Adobe PDF | 265 | View/Open |
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