Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling
Tetraspanin CD151 is increasingly implicated as a multifaceted mediator of cancer development and progression. Here we investigated the role of CD151 in breast cancer in the context of the Wnt oncogenic activation. Our data showed that removal of one or both of CD151 alleles in the MMTV-Wnt1 model s...
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Format: | Article |
Language: | English |
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Elsevier
2019-12-01
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Series: | Neoplasia: An International Journal for Oncology Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558619302787 |
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doaj-ea525d26453f49b59696b8033300e08f |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongxia Li Jieming Li Rongbo Han Xinyu Deng Junfong Shi Huanhuan Huang Nevean Hamad Abigail McCaughley Jinpeng Liu Chi Wang Kuey Chen Dongping Wei Jun Qiang Sean Thatcher Yadi Wu Chunming Liu Olivier Thibault Xiaowei Wei Song Chen Hai Qian Binhua P. Zhou Pao Xu Xiuwei H. Yang |
spellingShingle |
Hongxia Li Jieming Li Rongbo Han Xinyu Deng Junfong Shi Huanhuan Huang Nevean Hamad Abigail McCaughley Jinpeng Liu Chi Wang Kuey Chen Dongping Wei Jun Qiang Sean Thatcher Yadi Wu Chunming Liu Olivier Thibault Xiaowei Wei Song Chen Hai Qian Binhua P. Zhou Pao Xu Xiuwei H. Yang Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling Neoplasia: An International Journal for Oncology Research |
author_facet |
Hongxia Li Jieming Li Rongbo Han Xinyu Deng Junfong Shi Huanhuan Huang Nevean Hamad Abigail McCaughley Jinpeng Liu Chi Wang Kuey Chen Dongping Wei Jun Qiang Sean Thatcher Yadi Wu Chunming Liu Olivier Thibault Xiaowei Wei Song Chen Hai Qian Binhua P. Zhou Pao Xu Xiuwei H. Yang |
author_sort |
Hongxia Li |
title |
Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling |
title_short |
Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling |
title_full |
Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling |
title_fullStr |
Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling |
title_full_unstemmed |
Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signaling |
title_sort |
deletion of tetraspanin cd151 alters the wnt oncogene-induced mammary tumorigenesis: a cell type-linked function and signaling |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 |
publishDate |
2019-12-01 |
description |
Tetraspanin CD151 is increasingly implicated as a multifaceted mediator of cancer development and progression. Here we investigated the role of CD151 in breast cancer in the context of the Wnt oncogenic activation. Our data showed that removal of one or both of CD151 alleles in the MMTV-Wnt1 model significantly decreased the tumor-free survival of mice from 34 weeks on average to 22 weeks and 18 weeks, respectively. This effect coincided with an accelerated tumor growth and an increased number of Ki-67+ proliferative cells. Mechanistically, the CD151-deficient tumors were largely ER+, and exhibited hyperactivation of the Wnt pathway as reflected by a marked upregulation in β-catenin and Cyclin D1, and their target genes. In addition, E-cadherin displayed a cytosolic distribution and transcription factor Snail was markedly upregulated. Collectively, this data implies that CD151 suppresses the Wnt1-driven tumorigenesis, at least in part, via counteracting the epithelial-mesenchymal transition (EMT)-like program in luminal epithelial cells. Meanwhile, the proportion of tumor cells expressing CK5 or p63, the biomarkers of myoepithelial/basal cells, markedly decreased in the absence of CD151. This change was accompanied by a decreased invasiveness of tumors and their incompetence to form a long-term cell culture. Consistent with this basal cell-linked role, the CD151 downregulation impairs mammosphere formation in MCF-10A cells and the defect was rescued by re-expression of intact CD151 ORF, but not its integrin binding-defective mutant. Overall, our study suggests that CD151 is a key player in the Wnt oncogene-driven tumorigenesis and impacts breast cancer malignancy in a cell type-dependent manner. |
url |
http://www.sciencedirect.com/science/article/pii/S1476558619302787 |
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doaj-ea525d26453f49b59696b8033300e08f2020-11-25T01:49:10ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-12-01211211511163Deletion of tetraspanin CD151 alters the Wnt oncogene-induced mammary tumorigenesis: A cell type-linked function and signalingHongxia Li0Jieming Li1Rongbo Han2Xinyu Deng3Junfong Shi4Huanhuan Huang5Nevean Hamad6Abigail McCaughley7Jinpeng Liu8Chi Wang9Kuey Chen10Dongping Wei11Jun Qiang12Sean Thatcher13Yadi Wu14Chunming Liu15Olivier Thibault16Xiaowei Wei17Song Chen18Hai Qian19Binhua P. Zhou20Pao Xu21Xiuwei H. Yang22Freshwater Fisheries Research Center, Ministry of Agriculture, and Fisheries College, Nanjing Agricultural University, Wuxi, Jiangsu Province, PR China; Department of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KY; Center of Drug Discovery, China Pharmaceutical University, Nanjing, Jiangsu Province, PR ChinaDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KY; Department of Oncology, Nanjing Medical University, Nanjing, Jiangsu Province, PR ChinaDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Oncology, Nanjing Medical University, Nanjing, Jiangsu Province, PR ChinaDepartment of Oncology, Nanjing Medical University, Nanjing, Jiangsu Province, PR ChinaDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Oncology, Nanjing Medical University, Nanjing, Jiangsu Province, PR ChinaFreshwater Fisheries Research Center, Ministry of Agriculture, and Fisheries College, Nanjing Agricultural University, Wuxi, Jiangsu Province, PR ChinaDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KYDepartment of Oncology, Nanjing Medical University, Nanjing, Jiangsu Province, PR ChinaInstitute of Medicinal Biotechnology, Jiangsu College of Nursing, Huaian, Jiangsu Province, PR China; Corresponding authors.Center of Drug Discovery, China Pharmaceutical University, Nanjing, Jiangsu Province, PR China; Corresponding authors.Department of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KY; Corresponding authors.Freshwater Fisheries Research Center, Ministry of Agriculture, and Fisheries College, Nanjing Agricultural University, Wuxi, Jiangsu Province, PR China; Corresponding authors.Department of Pharmacology and Nutritional Sciences, Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky, Lexington, KY; Corresponding authors.Tetraspanin CD151 is increasingly implicated as a multifaceted mediator of cancer development and progression. Here we investigated the role of CD151 in breast cancer in the context of the Wnt oncogenic activation. Our data showed that removal of one or both of CD151 alleles in the MMTV-Wnt1 model significantly decreased the tumor-free survival of mice from 34 weeks on average to 22 weeks and 18 weeks, respectively. This effect coincided with an accelerated tumor growth and an increased number of Ki-67+ proliferative cells. Mechanistically, the CD151-deficient tumors were largely ER+, and exhibited hyperactivation of the Wnt pathway as reflected by a marked upregulation in β-catenin and Cyclin D1, and their target genes. In addition, E-cadherin displayed a cytosolic distribution and transcription factor Snail was markedly upregulated. Collectively, this data implies that CD151 suppresses the Wnt1-driven tumorigenesis, at least in part, via counteracting the epithelial-mesenchymal transition (EMT)-like program in luminal epithelial cells. Meanwhile, the proportion of tumor cells expressing CK5 or p63, the biomarkers of myoepithelial/basal cells, markedly decreased in the absence of CD151. This change was accompanied by a decreased invasiveness of tumors and their incompetence to form a long-term cell culture. Consistent with this basal cell-linked role, the CD151 downregulation impairs mammosphere formation in MCF-10A cells and the defect was rescued by re-expression of intact CD151 ORF, but not its integrin binding-defective mutant. Overall, our study suggests that CD151 is a key player in the Wnt oncogene-driven tumorigenesis and impacts breast cancer malignancy in a cell type-dependent manner.http://www.sciencedirect.com/science/article/pii/S1476558619302787 |