Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer
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...
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doaj-762fa4a77c0c47a0ba4d9787067d86a52020-11-25T03:04:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-01214473447310.3390/ijms21124473Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic CancerMei Jen Hsieh0Tai-Jan Chiu1Yu Chun Lin2Ching-Chieh Weng3Yu-Ting Weng4Chang-Chun Hsiao5Kuang-hung Cheng6Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDivision of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung 83301, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanPancreatic 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 KRAS<sup>G12D</sup> 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.https://www.mdpi.com/1422-0067/21/12/4473pancreatic ductal adenocarcinoma (PDAC)APCCD34cancer stemnessmetastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mei Jen Hsieh Tai-Jan Chiu Yu Chun Lin Ching-Chieh Weng Yu-Ting Weng Chang-Chun Hsiao Kuang-hung Cheng |
spellingShingle |
Mei Jen Hsieh Tai-Jan Chiu Yu Chun Lin Ching-Chieh Weng Yu-Ting Weng Chang-Chun Hsiao Kuang-hung Cheng Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer International Journal of Molecular Sciences pancreatic ductal adenocarcinoma (PDAC) APC CD34 cancer stemness metastasis |
author_facet |
Mei Jen Hsieh Tai-Jan Chiu Yu Chun Lin Ching-Chieh Weng Yu-Ting Weng Chang-Chun Hsiao Kuang-hung Cheng |
author_sort |
Mei Jen Hsieh |
title |
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer |
title_short |
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer |
title_full |
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer |
title_fullStr |
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer |
title_full_unstemmed |
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer |
title_sort |
inactivation of apc induces cd34 upregulation to promote epithelial-mesenchymal transition and cancer stem cell traits in pancreatic cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-06-01 |
description |
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 KRAS<sup>G12D</sup> 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. |
topic |
pancreatic ductal adenocarcinoma (PDAC) APC CD34 cancer stemness metastasis |
url |
https://www.mdpi.com/1422-0067/21/12/4473 |
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