MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway
Matrix Gla protein (MGP), an extracellular matrix protein, is mainly associated with the inhibition of calcification in skeleton, coronary artery, and kidney, and more recently it has also been implicated in cancer. However, the biological function of MGP inside cancer cells and its role in colon ca...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Molecular Therapy: Oncolytics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520300553 |
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doaj-b2297ecdb6b5452aa729251a0ee61216 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xueqing Li Rui Wei Mizhu Wang Li Ma Zheng Zhang Lei Chen Qingdong Guo Shuilong Guo Shengtao Zhu Shutian Zhang Li Min |
| spellingShingle |
Xueqing Li Rui Wei Mizhu Wang Li Ma Zheng Zhang Lei Chen Qingdong Guo Shuilong Guo Shengtao Zhu Shutian Zhang Li Min MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway Molecular Therapy: Oncolytics matrix Gla protein calcium signaling NF-κB proliferation colon cancer biomarker |
| author_facet |
Xueqing Li Rui Wei Mizhu Wang Li Ma Zheng Zhang Lei Chen Qingdong Guo Shuilong Guo Shengtao Zhu Shutian Zhang Li Min |
| author_sort |
Xueqing Li |
| title |
MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway |
| title_short |
MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway |
| title_full |
MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway |
| title_fullStr |
MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway |
| title_full_unstemmed |
MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway |
| title_sort |
mgp promotes colon cancer proliferation by activating the nf-κb pathway through upregulation of the calcium signaling pathway |
| publisher |
Elsevier |
| series |
Molecular Therapy: Oncolytics |
| issn |
2372-7705 |
| publishDate |
2020-06-01 |
| description |
Matrix Gla protein (MGP), an extracellular matrix protein, is mainly associated with the inhibition of calcification in skeleton, coronary artery, and kidney, and more recently it has also been implicated in cancer. However, the biological function of MGP inside cancer cells and its role in colon cancer (CC) remain largely unknown. MGP expression and its association with clinicopathologic characteristics in CC were analyzed by immunohistochemistry and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The effects of MGP on CC cell proliferation were evaluated via knockdown and overexpression experiments in vitro. Mechanisms of MGP in CC were explored by western blots, quantitative real-time PCR, Fluo-3 AM staining, Rhod-2 AM staining, immunofluorescence, and other techniques. Our study confirmed that MGP was upregulated in different stages of CC and associated with a worse prognosis. MGP could enrich intracellular free Ca2+ concentration and promote nuclear factor κB (NF-κB)/p65 phosphorylation, activating the expression of c-MYC, ICAM-1, and VEGFA. Furthermore, the reduction of intracellular free Ca2+ concentration and the subsequent growth inhibition effect on CC cells induced by small interfering RNA targeting MGP (siMGP) could be rescued by a higher calcium concentration environment. Therefore, MGP promotes the growth and proliferation of CC cells by enriching intracellular calcium concentration and activating the NF-κB pathway, and it could serve as a potential prognostic biomarker in CC patients. |
| topic |
matrix Gla protein calcium signaling NF-κB proliferation colon cancer biomarker |
| url |
http://www.sciencedirect.com/science/article/pii/S2372770520300553 |
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doaj-b2297ecdb6b5452aa729251a0ee612162020-11-25T03:12:23ZengElsevierMolecular Therapy: Oncolytics2372-77052020-06-0117371383MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling PathwayXueqing Li0Rui Wei1Mizhu Wang2Li Ma3Zheng Zhang4Lei Chen5Qingdong Guo6Shuilong Guo7Shengtao Zhu8Shutian Zhang9Li Min10Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China; Department of Gastroenterology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. ChinaDepartment of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China; Corresponding author: Shutian Zhang, PhD, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China.Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China; Corresponding author: Li Min, PhD, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P.R. China.Matrix Gla protein (MGP), an extracellular matrix protein, is mainly associated with the inhibition of calcification in skeleton, coronary artery, and kidney, and more recently it has also been implicated in cancer. However, the biological function of MGP inside cancer cells and its role in colon cancer (CC) remain largely unknown. MGP expression and its association with clinicopathologic characteristics in CC were analyzed by immunohistochemistry and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The effects of MGP on CC cell proliferation were evaluated via knockdown and overexpression experiments in vitro. Mechanisms of MGP in CC were explored by western blots, quantitative real-time PCR, Fluo-3 AM staining, Rhod-2 AM staining, immunofluorescence, and other techniques. Our study confirmed that MGP was upregulated in different stages of CC and associated with a worse prognosis. MGP could enrich intracellular free Ca2+ concentration and promote nuclear factor κB (NF-κB)/p65 phosphorylation, activating the expression of c-MYC, ICAM-1, and VEGFA. Furthermore, the reduction of intracellular free Ca2+ concentration and the subsequent growth inhibition effect on CC cells induced by small interfering RNA targeting MGP (siMGP) could be rescued by a higher calcium concentration environment. Therefore, MGP promotes the growth and proliferation of CC cells by enriching intracellular calcium concentration and activating the NF-κB pathway, and it could serve as a potential prognostic biomarker in CC patients.http://www.sciencedirect.com/science/article/pii/S2372770520300553matrix Gla proteincalcium signalingNF-κBproliferationcolon cancerbiomarker |