Lan Youmian, Liu Dongchen, Liang Bin, Song Xuhong, Xie Lingzhu, Peng Hanwei, Guo Haipeng, Hong Chaoqun, Weng Xuwu, Wei Xiaolong, Liao Xiaoqi, Liang Rui, Huang Dongyang, Liu Muyuan
Department of Head and Neck, Cancer Hospital of Shantou University Medical College, Shantou, China.
Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, China.
Ann Med. 2025 Dec;57(1):2483379. doi: 10.1080/07853890.2025.2483379. Epub 2025 Mar 26.
Studies have examined the role of integrin α3 (ITGA3) in papillary thyroid carcinoma (PTC). However, the functional and molecular mechanism by which ITGA3 is involved in the progression of PTC remains poorly understood.
To investigate the role of ITGA3 in PTC, raw PTC transcriptome data underwent comprehensive bioinformatics analyses, including differential expression, co-expression network, and enrichment analyses. ITGA3 expression was validated immunohistochemistry and western blotting in PTC tissues. Cell functional assays and xenograft models assessed PTC cell behaviour. The potential mechanisms of ITGA3 were elucidated using bioinformatics analyses, western blotting, co-immunoprecipitation, and immunofluorescence. Finally, integration of ITGA3 expression with clinical parameters enabled nomogram construction for precise prediction of cervical lymph node metastasis (CLNM) in PTC.
ITGA3 was upregulated in PTC and associated strongly with CLNM (79.5% 53.84%, = 0.016). ITGA3 expression enhanced PTC proliferation and migration and cooperating with the MET protein tyrosine kinase, followed by phosphorylation of MET at Tyr1234/1235, and activation of ERK and PI3K/AKT signaling pathways. Furthermore, upregulation ITGA3 reduced phosphorylation at FAK-Tyr397 and Src-Tyr416 in PTC cells. Finally, a nomogram combining ITGA3 expression and clinical parameters for predicting CLNM was constructed and validated, achieving a ROC curve AUC of 0.719, suggesting potential application for PTC diagnosis.
ITGA3 promotes PTC cell proliferation and migration by cooperating with MET to activate MET-ERK and MET-PI3K-AKT signalling. ITGA3-MET cooperation may serve as a potential therapeutic target.
已有研究探讨整合素α3（ITGA3）在甲状腺乳头状癌（PTC）中的作用。然而，ITGA3参与PTC进展的功能和分子机制仍知之甚少。
为研究ITGA3在PTC中的作用，对原始PTC转录组数据进行了全面的生物信息学分析，包括差异表达、共表达网络和富集分析。通过免疫组织化学和蛋白质印迹法验证PTC组织中ITGA3的表达。细胞功能实验和异种移植模型评估PTC细胞行为。利用生物信息学分析、蛋白质印迹法、免疫共沉淀和免疫荧光法阐明ITGA3的潜在机制。最后，将ITGA3表达与临床参数相结合，构建列线图以精确预测PTC中的颈部淋巴结转移（CLNM）。
ITGA3在PTC中上调，并与CLNM密切相关（79.5%对53.84%，P = 0.016）。ITGA3表达增强了PTC的增殖和迁移，并与MET蛋白酪氨酸激酶协同作用，随后MET在Tyr1234/1235位点磷酸化，激活ERK和PI3K/AKT信号通路。此外，ITGA3的上调降低了PTC细胞中FAK-Tyr397和Src-Tyr416的磷酸化水平。最后，构建并验证了一个结合ITGA3表达和临床参数预测CLNM的列线图，ROC曲线下面积为0.719，表明其在PTC诊断中具有潜在应用价值。
ITGA3通过与MET协同激活MET-ERK和MET-PI3K-AKT信号促进PTC细胞增殖和迁移。ITGA3-MET协同作用可能是一个潜在的治疗靶点。
