Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signalling pathway in breast cancer cells

Cong, Yizi, Cui, Yuxin, Zhu, Shiguang, Cao, Jianqiao, Zou, Haidong, Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908, Qiao, Guangdong, Jiang, Wenguo ORCID: https://orcid.org/0000-0002-3283-1111 and Yu, Zhigang 2020. Tim-3 promotes cell aggressiveness and paclitaxel resistance through the NF-κB /STAT3 signalling pathway in breast cancer cells. Chinese Journal of Cancer Research 32 (5) , pp. 564-579. 10.21147/j.issn.1000-9604.2020.05.02

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Abstract

Objective: Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated. Methods: Tim-3 gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells. Results: In a pooled analysis of The Cancer Genome Atlas (TCGA) database, Tim-3 gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3low breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (CCND1), C-Myc, matrix metalloproteinase-1(MMP1), TWIST, vascular endothelial growth factor (VEGF) upregulation, concomitant with E-cadherin downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression. Conclusions: Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer Verlag
ISSN:	1000-9604
Date of First Compliant Deposit:	6 October 2020
Date of Acceptance:	26 September 2020
Last Modified:	04 Dec 2024 06:30
URI:	https://orca.cardiff.ac.uk/id/eprint/135326

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