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ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway

Authors Yang L, Wang Y, Sun R, Zhang Y, Fu Y, Zheng Z, Ji Z, Zhao D

Received 7 November 2019

Accepted for publication 2 March 2020

Published 17 March 2020 Volume 2020:13 Pages 2299—2309

DOI https://doi.org/10.2147/OTT.S237751

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su


Longyan Yang,1,* Yan Wang,1,* Rongxin Sun,1,* Yuanyuan Zhang,1 Ying Fu,1 Zhaohui Zheng,1 Zhili Ji,2 Dong Zhao1

1Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Luhe Hospital Capital Medical University, Beijing 101149, People’s Republic of China; 2Department of General Surgery, Luhe Hospital Capital Medical University, Beijing 101149, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Dong Zhao; Zhili Ji
Tel +86-10-69543901
Fax +86-10-69531069
Email zhaodong@ccm.edu.cn; lhyyjzl@163.com

Purpose: Although papillary thyroid carcinoma (PTC) is associated with a generally favorable prognosis, about 15% of patients present recurrence and distant metastasis in the next decade leading to death. Angiopoietin-like 4 (ANGPTL4) is secreted to circulation and belongs to the angiopoietin-like proteins. The expression of ANGPTL4 was increased in several solid tumor tissues compared to corresponding paracancerous tissues. ANGPTL4 was identified as pro-tumorigenic protein, including stimulating tumor cell growth, promoting tumor metastasis. However, the clinical significance and biological function of ANGPTL4 in PTC is still unclear. Hence, the purpose of this study was to evaluate the role of ANGPTL4 in PTC, investigating the possibility of whether ANGPTL4 could become a novel target for PTC therapy.
Methods: We investigated the expression level of ANGPTL4 and pAKT in PTC and paracancerous tissue by immunohistochemistry. We determined the effect of ANGPTL4 in PTC cell proliferation through cell counting kit-8 (CCK-8) and cell cycle by flow cytometry analysis. Furthermore, the correlation between ANGPTL4 expression levels and PTC cell proliferation from the TCGA data set was analyzed by GSEA. We explored the role of ANGPTL4 on the phosphorylation of AKT and proliferation in PTC cells via overexpression or knockdown assays and AKT inhibitor assay.
Results: In the present study, we found that ANGPTL4 was highly expressed in both protein and mRNA level in PTC compared with adjacent noncancerous tissues or benign nodule. ANGPTL4 expression increased according to thyroid tumor progression. ANGPTL4 level was positively correlated with the size of PTC. ANGPTL4 increased cell proliferation and decreased cell cycle arrest of PTC. Knockdown of ANGPTL4 inhibited the phosphorylation of AKT. ANGPTL4 regulated PTC cell proliferation through AKT signaling pathway.
Conclusion: Our findings suggested that ANGPTL4 was increased in PTC compared with adjacent noncancerous tissues, and ANGPTL4 increased cell proliferation and inhibited cell cycle arrest in PTC cells via promoting AKT phosphorylation. The study may provide fundamental information to suggest its suitability as a target for the treatment of PTC.

Keywords: papillary thyroid carcinoma, angiopoietin-like 4, AKT, proliferation

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