{"title":"PINCH-1 promotes tumor growth and metastasis by enhancing DRP1-mediated mitochondrial fission in head and neck squamous cell carcinoma.","authors":"Ruxian Tian, Hao Song, Jiaxuan Li, Ting Yuan, Jiahui Liu, Yaqi Wang, Yumei Li, Xicheng Song","doi":"10.1080/15384047.2025.2477365","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Abnormal expression of PINCH-1 has been observed in various types of human cancers. However, the clinical importance and mechanism underlying its role in head and neck squamous cell carcinoma (HNSCC) is yet to be fully elucidated.</p><p><strong>Methods: </strong>This study evaluated the expression of PINCH-1 in HNSCC samples through immunohistochemical staining and Western blotting. AMC-HN-8, Cal27, and SCC7 cell lines were utilized for cellular function experiments, both in vivo and in vitro. CCK8, colony-formation assay, flow cytometry, wound-healing assay, and transwell assay were employed to investigate the effects of alterations in target proteins on the growth and metastasis of cancer cells. Mito-Tracker Deep Red FM was used to track mitochondrial morphology.</p><p><strong>Results: </strong>PINCH-1 was found to be overexpressed in HNSCC and closely associated with lymph node metastasis and poor pathologic differentiation. Its upregulation promoted proliferation, inhibited apoptosis, and enhanced migration and invasion in HNSCC cells. It also promoted mitochondrial fission. We conducted a mechanism analysis, which showed that PINCH-1 knockdown inhibited mitochondrial fission by reducing the expression of DRP1. Furthermore, inhibition of mitochondrial fission could impede the proliferation and metastasis of HNSCC cells. Re-expression of DRP1 reversed the inhibitory effect of PINCH-1 knockdown on mitochondrial fission, cell proliferation, and metastasis in HNSCC cells.</p><p><strong>Conclusions: </strong>PINCH-1 plays a critical oncogenic role in HNSCC by enhancing DRP1-mediated mitochondrial fission, which may serve as a novel therapeutic target for HNSCC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2477365"},"PeriodicalIF":4.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901378/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15384047.2025.2477365","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/11 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Abnormal expression of PINCH-1 has been observed in various types of human cancers. However, the clinical importance and mechanism underlying its role in head and neck squamous cell carcinoma (HNSCC) is yet to be fully elucidated.
Methods: This study evaluated the expression of PINCH-1 in HNSCC samples through immunohistochemical staining and Western blotting. AMC-HN-8, Cal27, and SCC7 cell lines were utilized for cellular function experiments, both in vivo and in vitro. CCK8, colony-formation assay, flow cytometry, wound-healing assay, and transwell assay were employed to investigate the effects of alterations in target proteins on the growth and metastasis of cancer cells. Mito-Tracker Deep Red FM was used to track mitochondrial morphology.
Results: PINCH-1 was found to be overexpressed in HNSCC and closely associated with lymph node metastasis and poor pathologic differentiation. Its upregulation promoted proliferation, inhibited apoptosis, and enhanced migration and invasion in HNSCC cells. It also promoted mitochondrial fission. We conducted a mechanism analysis, which showed that PINCH-1 knockdown inhibited mitochondrial fission by reducing the expression of DRP1. Furthermore, inhibition of mitochondrial fission could impede the proliferation and metastasis of HNSCC cells. Re-expression of DRP1 reversed the inhibitory effect of PINCH-1 knockdown on mitochondrial fission, cell proliferation, and metastasis in HNSCC cells.
Conclusions: PINCH-1 plays a critical oncogenic role in HNSCC by enhancing DRP1-mediated mitochondrial fission, which may serve as a novel therapeutic target for HNSCC.
目的：在多种类型的人类癌症中发现了PINCH-1的异常表达。然而，其在头颈部鳞状细胞癌（HNSCC）中的临床重要性和作用机制尚未完全阐明。方法：采用免疫组化染色和Western blotting检测PINCH-1在HNSCC中的表达。利用AMC-HN-8、Cal27和SCC7细胞系进行体内和体外细胞功能实验。采用CCK8、集落形成实验、流式细胞术、伤口愈合实验和transwell实验研究靶蛋白的改变对癌细胞生长和转移的影响。使用Mito-Tracker Deep Red FM跟踪线粒体形态。结果：PINCH-1在HNSCC中过表达，与淋巴结转移和病理分化不良密切相关。其上调可促进HNSCC细胞增殖，抑制凋亡，增强迁移和侵袭。它还促进了线粒体裂变。我们进行了机制分析，发现PINCH-1敲低通过降低DRP1的表达抑制线粒体裂变。此外，抑制线粒体分裂可以抑制HNSCC细胞的增殖和转移。DRP1的重新表达逆转了PINCH-1敲低对HNSCC细胞线粒体分裂、细胞增殖和转移的抑制作用。结论：PINCH-1通过增强drp1介导的线粒体分裂，在HNSCC中起关键的致癌作用，可能成为HNSCC新的治疗靶点。
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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