CXCR4 promotes migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma by activating STAT3 signaling pathway

• Published in: Journal of cancer research and therapeutics Vol. 20; no. 4; pp. 1241 - 1250
• Main Authors: Hu, Yajie, Xu, Zhipeng, Zhou, Dongsheng, Hou, Haitao, Liu, Bin, Long, Houlong, Hu, Wenxin, Tang, Yuanqi, Wang, Jianning, Wei, Dan, Zhao, Quanlin
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer - Medknow 01.08.2024; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Edition: 2
• Subjects: Animals; Cell Line, Tumor; Cell Movement; Cell Proliferation; Development and progression; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Humans; Lung cancer; Male; Metastasis; Mice; Middle Aged; Neoplasm Invasiveness; Original Article; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Thyroid cancer; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - metabolism; Thyroid Cancer, Papillary - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Xenograft Model Antitumor Assays; China; migration; CXCR4; invasion; papillary thyroid cancer; STAT3
• ISSN: 0973-1482; 1998-4138; 1998-4138
• DOI: 10.4103/jcrt.jcrt_2395_22

ABSTRACT Aims: Papillary thyroid cancer (PTC) is a serious threat to human health worldwide, while metastasis in the early phase limits therapeutic success and leads to poor survival outcomes. The CXC chemokine receptor type 4 (CXCR4) plays an important role in many cellular movements such as transcriptional modulation, cell skeleton rearrangement, and cell migration, and the change in CXCR4 levels are crucial in various diseases including cancer. In this study, we explored the role of CXCR4 in the migration and invasion of PTC and investigated the potential mechanisms underlying its effects. Subjects and Methods: We analyzed the expression levels of CXCR4 in PTC tissues and cell lines. Would healing migration, Transwell invasion assay in vitro, and tail-vein lung metastasis assay In vivo were performed to evaluated the migration and invasion abilities of PTC cells with stable CXCR4 knockdown or overexpression. Signal transducers and activators of transcription (STAT3) signaling pathway-related protein expressions were examined by Western blotting assays. Results: The results showed that CXCR4 was highly expressed in PTC cell lines and PTC tissues. CXCR4 knockdown in PTC cells dampened the migration, invasion, and epithelial-mesenchymal transition (EMT), whereas CXCR4 overexpression enhanced these properties. In vivo, we also found that CXCR4 promoted the metastasis of PTC. Mechanistic studies showed that CXCR4 played these vital roles through the STAT3 signaling pathway. Furthermore, PTC patients with high CXCR4 or p-STAT3 expression correlated with aggressive clinical characteristics such as extrathyroidal extension (ETE), and lymph node metastasis (LNM). Conclusions: We provided evidence that CXCR4 might activate the STAT3 signaling pathway and further promote PTC development. Thus, CXCR4 might be a novel therapeutic target for PTC.