整合素家族在头颈部鳞癌进展及其肿瘤微环境调控中的作用

doi:10.3870/j.issn.1672-8009.2026.03.013

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (3): 331-336.doi: 10.3870/j.issn.1672-8009.2026.03.013

整合素家族在头颈部鳞癌进展及其肿瘤微环境调控中的作用

孙远远¹, 孙睿^1,2, 王健豪¹

¹山西医科大学口腔医学院·口腔医院太原市,030001
²山西白求恩医院(山西医学科学院,同济山西医院)山西医科大学第三医院口腔科太原市,030032

收稿日期:2025-10-29 发布日期:2026-06-01
通讯作者: 孙睿(E-mail:sunrui@sxbqeh.com.cn)
基金资助:
山西省自然科学基金(No.202103021224378)

Role of Integrin Family in Progression of Head and Neck Squamous Cell Carcinoma and Regulation of Its Tumor Microenvironment

SUN Yuanyuan¹, SUN Rui^1,2, WANG Jianhao¹

¹School and Hospital of Stomatology,Shanxi Medical University,Taiyuan,030001,China
²Department of Stomatology,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan,030032,China

Received:2025-10-29 Published:2026-06-01
Contact: SUN Rui(E-mail:sunrui@sxbqeh.com.cn)
Supported by:
Natural Science Foundation of Shanxi Province(No.202103021224378).

摘要/Abstract

摘要： 整合素是一类异二聚体跨膜受体,通过与肿瘤微环境相互作用并调节Wnt/β-连环蛋白、FAK和MAPK等信号通路,在介导肿瘤生长、侵袭和耐药性方面发挥关键作用。许多研究表明,在头颈部鳞癌中,部分整合素的表达水平与疾病的恶性进展和预后密切相关。文章就关键整合素在头颈部鳞癌恶性进展及耐药中的作用及其在肿瘤微环境中介导肿瘤细胞与免疫细胞和基质细胞的多维度通讯做一综述。

关键词: 整合素, 头颈部鳞状细胞癌, 肿瘤微环境

Abstract: Integrins are a class of heterodimeric transmembrane receptors that play a pivotal role in mediating tumor growth,invasion,and drug resistance by interacting with the tumor microenvironment and regulating signaling pathways such as Wnt/β-catenin,FAK,and MAPK.Numerous studies have demonstrated that the expression levels of certain integrins in head and neck squamous cell carcinoma(HNSCC)are closely associated with malignant progression and prognosis.This article reviews the roles of key integrins in the malignant progression and drug resistance of HNSCC,as well as their multidimensional communication between tumor cells,immune cells,and stromal cells within the tumor microenvironment.

Key words: integrin, head and neck squamous cell carcinoma, tumor microenvironment

中图分类号:

R739.91

孙远远, 孙睿, 王健豪. 整合素家族在头颈部鳞癌进展及其肿瘤微环境调控中的作用[J]. 医学分子生物学杂志, 2026, 23(3): 331-336.

SUN Yuanyuan, SUN Rui, WANG Jianhao. Role of Integrin Family in Progression of Head and Neck Squamous Cell Carcinoma and Regulation of Its Tumor Microenvironment[J]. Journal of Medical Molecular Biology, 2026, 23(3): 331-336.

参考文献

[1] HEINOLAINEN A,NGUYEN B,SILÉN S,et al.Survival and data-driven phenotypes in head and neck cancer[J].Sci Rep,2025,15(1):5985.
[2] PUNOVUORI K,BERTILLOT F,MIROSHNIKOVA Y A,et al.Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer[J].Cell,2024,187(25):7267-7284.e20.
[3] 冯阳光,杨东霖,李星慧,等.整合素受体在肾脏疾病中的作用及机制[J].肾脏病与透析肾移植杂志,2025,34(4):365-370.
FENG Y G,YANG D L,LI X H,et al.The role and molecular mechanisms of integrin receptors in renal disorders[J].Chin J Nephrol Dial Transplant,2025,34(4):365-370.
[4] 赵瑞,华清泉.整合素αvβ6在头颈部鳞状细胞癌中的作用研究[J].中国中西医结合耳鼻咽喉科杂志,2023,31(3):189-194,209.
ZHAO R,HUA Q Q.The role of integrin αvβ6 in head and neck squamous cell carcinoma[J].Chin J Otorhinolaryngol Integr Med,2023,31(3):189-194,209.
[5] ZOU C,ZHU J,XIONG J,et al.Comprehensive characterization of the integrin family across 32 cancer types[J].Genomics Proteomics Bioinformatics,2024,22(4):qzae035.
[6] XU L,BARRETT J G,PENG J,et al.ITGAV promotes the progression of head and neck squamous cell carcinoma[J].Curr Oncol,2024,31(3):1311-1322.
[7] KAMARAJAN P,ATEIA I,SHIN J M,et al.Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin[J].PLoS Pathog,2020,16(10):e1008881.
[8] NAKAMURA T,SHINRIKI S,JONO H,et al.Osteopontin-integrin α(v)β(3)axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma[J].FEBS Lett,2015,589(2):231-239.
[9] ROUTILA E,SALMINEN S,MAHRAN R,et al.Evaluation of integrin glycovariants as biomarkers of metastasis,invasion,and therapy stratification in head and neck squamous cell carcinoma[J].Cancer Med,2025,14(9):e70717.
[10] QI X,ZHOU J,WANG P,et al.KLF7-regulated ITGA2 as a therapeutic target for inhibiting oral cancer stem cells[J].Cell Death Dis,2025,16(1):354.
[11] LIU J,WANG Y,CHEN X,et al.ITGA5 is associated with prognosis marker and immunosuppression in head and neck squamous cell carcinoma[J].Diagn Pathol,2024,19(1):134.
[12] LI D P,SUN A J,ZHANG L,et al.Elevated ITGA5 facilitates hyperactivated mTORC1-mediated progression of laryngeal squamous cell carcinoma via upregulation of EFNB2[J].Theranostics,2022,12(17):7431-7449.
[13] RYU M H,PARK H M,CHUNG J,et al.Hypoxia-inducible factor-1 alpha mediates oral squamous cell carcinoma invasion via upregulation of alpha5 integrin and fibronectin[J].Biochem Biophys Res Commun,2010,393(1):11-15.
[14] ZHAO X,MAI Z,LIU L,et al.Hypoxia-driven TNS4 fosters HNSCC tumorigenesis by stabilizing integrin α5β1 complex and triggering FAK-mediated Akt and TGFβ signaling pathways[J].Int J Biol Sci,2024,20(1):231-248.
[15] ANGGRADITA L D,KIM J H,KIM M K,et al.Targeting the integrin beta 1-focal adhesion kinase axis with artemisinin:Biophysical disruption of cell adhesion,migration,and invasion in tongue cancer[J].VIEW,2025,6(2):20240089.
[16] PARK S J,MIN H J,YOON C,et al.Integrin β1 regulates the perineural invasion and radioresistance of oral squamous carcinoma cells by modulating cancer cell stemness[J].Cell Signal,2023,110:110808.
[17] KOROVINA I,ELSER M,BORODINS O,et al.β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3 D HNSCC models[J].Biomed Pharmacother,2024,171:116217.
[18] JIANG W,CHEN L,LI R,et al.Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma:a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker[J].BMC Med,2024,22(1):314.
[19] NGUYEN J,CHONG T W,ELMI H,et al.Role of hemidesmosomes in oral carcinogenesis:A systematic review[J].Cancers,2023,15(9):2533.
[20] SCHINKE H,SHI E,LIN Z,et al.A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer[J].Mol Cancer,2022,21(1):178.
[21] ZHOU J,HE M,ZHAO Q,et al.EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer[J].Mol Cancer,2025,24(1):94.
[22] AGUDO J,AGUIRRE-GHISO J A,BHATIA M,et al.Targeting cancer cell dormancy[J].Nat Rev Cancer,2024,24(2):97-104.
[23] PAN S,LIU H,XIAO H,et al.ITGB6 promotes tumor recurrence and metastasis by mediating the resistance of daughter cells of PGCCs to anoikis:ITGB6 promotes tumor recurrence and metastasis via Anoikis resistance[J].Sci Rep,2025,15(1):33571.
[24] SAKURAI S,ISHIDA Y,SHINTANI T,et al.Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma:a retrospective observational study[J].Pathol Oncol Res,2024,30:1611571.
[25] WANG S H,CHEN Y L,HUANG S H,et al.Tumor cell-derived ISG15 promotes fibroblast recruitment in oral squamous cell carcinoma via CD11 a-dependent glycolytic reprogramming[J].Oncogenesis,2025,14(1):6.
[26] ZHANG X,DONG Y,ZHAO M,et al.ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system[J].Theranostics,2020,10(26):12044-12059.
[27] ZHANG H R,QIAN Y M,ZHANG Y,et al.Multi-omics analysis deciphers intercellular communication regulating oxidative stress to promote oral squamous cell carcinoma progression[J].NPJ Precis Oncol,2024,8(1):272.
[28] LI J,LI S,SHU M,et al.Unravelling the heterogeneity of oral squamous cell carcinoma by integrative analysis of single-cell and bulk transcriptome data[J].J Cell Mol Med,2024,28(3):e18108.
[29] RAJTHALA S,MIN A,PARAJULI H,et al.Profiling and functional analysis of microRNA deregulation in cancer-associated fibroblasts in oral squamous cell carcinoma depicts an anti-invasive role of microRNA-204 via regulation of their motility[J].Int J Mol Sci,2021,22(21):11960.
[30] LIU X,LI J,YANG X,et al.Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling[J].Int J Oral Sci,2023,15(1):32.
[31] LI X,ZHAO H,JIANG E,et al.ITGB1/FERMT1 mechanoactivation enhances CD44 characteristic stemness in oral squamous cell carcinoma via ubiquitin-dependent CK1α degradation[J].Oncogene,2025,44(20):1530-1544.
[32] WANG S H,LIOU G G,LIU S H,et al.Laminin γ2-enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via integrin α3-dependent uptake by lymphatic endothelial cells[J].Int J Cancer,2019,144(11):2795-2810.
[33] ISHIYAMA T,SANO D,TAKAHASHI H,et al.Ligand-receptor interactions between squamous and endothelial cells induce head and neck squamous cell carcinoma[J].Cancer Sci,2025,116(8):2296-2305.
[34] YOU B,PAN S,GU M,et al.Extracellular vesicles rich in HAX1 promote angiogenesis by modulating ITGB6 translation[J].J Extracell Vesicles,2022,11(5):e12221.
[35] 徐潇奕,王斌,杨檬檬,等.肿瘤相关的巨噬细胞在口腔癌中的促癌机制[J].中国肿瘤临床,2025,52(15):783-790.
XU X Y,WANG B,YANG M M,et al.Pro-tumorigenic mechanisms of tumor-associated macrophages in oral cancer[J].Chin J Clin Oncol,2025,52(15):783-790.
[36] ZHANG C,LI K,ZHU H,et al.ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4⁺ macrophage infiltration[J].Nat Commun,2024,15(1):7077.
[37] GUO C,SUN H,DU Y,et al.Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization[J].J Exp Clin Cancer Res,2025,44(1):1.
[38] EKSTEDT S,CARDENAS E I,PIERSIALA K,et al.CD18 and CD36 expression in neutrophils from tumors and tumor-draining lymph nodes:Implications for metastasis in oral squamous cell carcinoma[J].Clin Exp Metastasis,2025,42(4):37.

整合素家族在头颈部鳞癌进展及其肿瘤微环境调控中的作用

Role of Integrin Family in Progression of Head and Neck Squamous Cell Carcinoma and Regulation of Its Tumor Microenvironment

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