The Suppressing Effects of Dkk3 Expression on Aggressiveness and Tumorigenesis of Colorectal Cancer
Autor: | Chang-Lai Hao, Hua-Chuan Zheng, Hua-Mao Jiang, Shuang Zhao, En-Hong Zhao |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Chemokine Colorectal cancer pathological behaviors colorectal cancer Biology medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine medicine Cell adhesion Original Research Cell growth aggressive phenotypes Cancer Dkk3 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease tumorigenesis 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein prognosis Carcinogenesis |
Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 10 (2020) |
ISSN: | 2234-943X |
DOI: | 10.3389/fonc.2020.600322 |
Popis: | Dkk3 has been discovered during comparison of immortalized and parental cells. Its expression has been shown to reduce colony formation and induce apoptosis of cancer cells, acting as a tumor suppressor. Herein, we demonstrate that Dkk3 overexpression or protein treatment may inhibit colorectal cancer cell proliferation, migration, and invasion and that they may promote apoptosis and G2 phase arrest with hypoexpression of Bcl-2, cdc25B, cdc25c, N-cadherin, slug, and twist and hyperexpression of Bax and E-cadherin. This effect is consistent with that of recombinant Dkk3 exposure and blocked with anti-Dkk3 antibody. Dkk3 deletion in intestinal cells was not associated with the emergence of epithelial lesions; however, adenoma emerged after sodium desoxycholate treatment. At both mRNA and protein levels, Dkk3 expression was higher in normal than in cancer tissues (pDkk3 mRNA expression was negatively associated with its promoter methylation, growth pattern, differentiation, and favorable prognosis in the patients with colorectal cancer (pDkk3-related signal pathways in colorectal cancer included those of cellular adhesion and migration, melanogenesis, chemokine, Hedgehog, JAK-STAT, TOLL-like receptor, TGF-β, MAPK, and calcium signaling (p |
Databáze: | OpenAIRE |
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