MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway

Xueqing Li; Rui Wei; Mizhu Wang; Li Ma; Zheng Zhang; Lei Chen; Qingdong Guo; Shuilong Guo; Shengtao Zhu; Shutian Zhang; Li Min

Molecular Therapy: Oncolytics (Jun 2020)

MGP Promotes Colon Cancer Proliferation by Activating the NF-κB Pathway through Upregulation of the Calcium Signaling Pathway

Xueqing Li,
Rui Wei,
Mizhu Wang,
Li Ma,
Zheng Zhang,
Lei Chen,
Qingdong Guo,
Shuilong Guo,
Shengtao Zhu,
Shutian Zhang,
Li Min

Affiliations

Xueqing Li: 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, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Rui Wei: 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
Mizhu Wang: 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
Li Ma: Department of Gastroenterology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Zheng Zhang: 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
Lei Chen: 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
Qingdong Guo: 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
Shuilong Guo: 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
Shengtao Zhu: 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
Shutian Zhang: 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: 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.
Li Min: 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.

Journal volume & issue: Vol. 17
pp. 371 – 383

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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