Yang Fan, Zhou Ying, Zhang You, Wei Weideng, Huang Fei, Yang Dan, Zhang Yixin, Zhang Ruiyang, Xia Xiaoqiang, Chen Qianming, Jiang Yuchen, Feng Xiaodong
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2025 Mar 28;26(7):3147. doi: 10.3390/ijms26073147.
Despite significant progress in characterizing the omics landscape of head and neck squamous cell carcinoma (HNSCC), the development of precision therapies remains limited. One key factor contributing to this challenge is the marked molecular heterogeneity of HNSCC. Further investigation of molecular profiles within HNSCC may facilitate the improvement in more effective precision treatments. Here, we focus on the dysregulation of PDZ and LIM domain protein 3 (PDLIM3) in HNSCC. The expression levels of PDLIM3 were analyzed using public datasets to assess its potential role in tumor progression. We found that PDLIM3 was downregulated in pan-cancer and HNSCC. The prognostic significance of PDLIM3 was evaluated through tissue microarray, and the downregulation of PDLIM3 was correlated with poor HNSCC prognosis. Investigating the implications of PDLIM3 for tumor metastatic ability in vitro, we found that PDLIM3 suppressed the migration and invasion of HNSCC, accompanied by partially impeding the process of epithelial-mesenchymal transition (EMT). Furthermore, PDLIM3 inhibited the transcriptional activity of Yes-associated protein (YAP), suggesting that YAP may be involved in the PDLIM3-mediated suppression of HNSCC metastatic ability. Our findings identify a potential signaling axis wherein PDLIM3 regulates YAP-EMT, thereby influencing tumor metastatic ability, and suggest the potential role of PDLIM3 as a tumor suppressor and prognostic biomarker for HNSCC.
尽管在表征头颈部鳞状细胞癌（HNSCC）的组学格局方面取得了重大进展，但精准治疗的发展仍然有限。导致这一挑战的一个关键因素是HNSCC显著的分子异质性。对HNSCC内分子谱的进一步研究可能有助于改进更有效的精准治疗。在此，我们聚焦于HNSCC中PDZ和LIM结构域蛋白3（PDLIM3）的失调。使用公共数据集分析PDLIM3的表达水平，以评估其在肿瘤进展中的潜在作用。我们发现PDLIM3在泛癌和HNSCC中表达下调。通过组织芯片评估PDLIM3的预后意义，发现PDLIM3的下调与HNSCC的不良预后相关。在体外研究PDLIM3对肿瘤转移能力的影响时，我们发现PDLIM3抑制HNSCC的迁移和侵袭，同时部分阻碍上皮-间质转化（EMT）过程。此外，PDLIM3抑制Yes相关蛋白（YAP）的转录活性，表明YAP可能参与PDLIM3介导的对HNSCC转移能力的抑制。我们的研究结果确定了一个潜在的信号轴，其中PDLIM3调节YAP-EMT，从而影响肿瘤转移能力，并提示PDLIM3作为HNSCC肿瘤抑制因子和预后生物标志物的潜在作用。
