Molecular mechanisms of mechanical stretching in regulating lung cancer cell behavior

doi:10.13418/j.issn.1001-165x.2025.4.13

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Chinese Journal of Clinical Anatomy ›› 2025, Vol. 43 ›› Issue (4) : 444-459. DOI: 10.13418/j.issn.1001-165x.2025.4.13

Molecular mechanisms of mechanical stretching in regulating lung cancer cell behavior

Li Xiangtian¹, Wen Xiaohui², Wang Ruolin², Cheng Yunshui³, Liu Zhaoru³, Lv Ying³, Fan Tingyu⁴*, Gong Fengying³*

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Abstract

Objective To elucidate the potential mechanisms linking cyclic mechanical stress to lung tumorigenesis. Methods The GEO dataset GSE272292 was re-analyzed to investigate the effects of cyclic tensile stress (15% strain, 0.2 Hz, applied for 7 days) on gene expression in A549 lung adenocarcinoma cells under stiff matrix conditions. Results Functional enrichment analysis revealed that differentially expressed genes were significantly enriched in "mitochondrial inner membrane" (a hub for energy metabolism) and "collagen-containing extracellular matrix". Key candidate genes, including mitochondrial ribosomal protein (MRPL13) and collagen type V (COL5A1), were identified as regulators of these dual phenotypes. GSEA further highlighted activation of "CD22-mediated B-cell receptor signaling regulation" pathway. Conclusions These findings suggest that mechanical signals may drive phenotypic alterations in mitochondrial energy metabolism and extracellular matrix (ECM) remodeling via MRPL13 and COL5A1, offering novel insights into lung cancer mechanobiology.

Key words

Mechanical stretching / Lung cancer / Mitochondrial metabolism / Extracellular matrix remodeling

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Li Xiangtian, Wen Xiaohui, Wang Ruolin, Cheng Yunshui, Liu Zhaoru, Lv Ying, Fan Tingyu, Gong Fengying. Molecular mechanisms of mechanical stretching in regulating lung cancer cell behavior[J]. Chinese Journal of Clinical Anatomy. 2025, 43(4): 444-459 https://doi.org/10.13418/j.issn.1001-165x.2025.4.13

References

[1] Najrana T, Mahadeo A, Abu-eid R, et al. Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells [J]. J Cell Physiol, 2020, 235(11): 8210-8223. DOI: 10.1002/jcp.29476.
[2] Roshanzadeh A, Nguyen TT, Nguyen KD, et al. Mechanoadaptive organization of stress fiber subtypes in epithelial cells under cyclic stretches and stretch release [J]. Sci Rep, 2020, 10(1): 18684. DOI: 10.1038/s41598-020-75791-2.
[3] Gong F, Yang Y, Wen L, et al. An overview of the role of mechanical stretching in the progression of lung cancer [J]. Front Cell Dev Biol, 2021, 9: 781828. DOI: 10.3389/fcell.2021.781828.
[4] Wang C, Yang J. Mechanical forces: The missing link between idiopathic pulmonary fibrosis and lung cancer [J]. Eur J Cell Biol, 2022, 101(3): 151234. DOI: 10.1016/j.ejcb.2022.151234.
[5] Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction [J]. Nature, 2011, 474(7350): 179-183. DOI: 10.1038/nature10137.
[6] Douguet D, Honoré E. Mammalian mechanoelectrical transduction: structure and function of force-gated ion channels [J]. Cell, 2019, 179(2): 340-354. DOI: 10.1016/j.cell.2019.08.049.
[7] Nakamura F, Song M, Hartwig JH, et al. Documentation and localization of force-mediated filamin A domain perturbations in moving cells [J]. Nat Commun, 2014, 5: 4656. DOI: 10.1038/ncomms5656.
[8] Pan J, Copland I, Post M, et al. Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development [J]. Am J Physiol Lung Cell Mol Physiol, 2006, 290(1): L185-L193. DOI: 10.1152/ajplung.00167.2005.
[9] Chess PR, Toia L, Finkelstein JN. Mechanical strain-induced proliferation and signaling in pulmonary epithelial H441 cells [J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(1): L43-L51. DOI: 10.1152/ajplung.2000.279.1.L43.
[10]Chaturvedi LS, Marsh HM, Basson MD. Src and focal adhesion kinase mediate mechanical strain-induced proliferation and ERK1/2 phosphorylation in human H441 pulmonary epithelial cells [J]. Am J Physiol Cell Physiol, 2007, 292(5): C1701-C1713. DOI: 10.1152/ajpcell.00529.2006.
[11]Wang WH, Hsu CL, Huang HC, et al. Quantitative phosphoproteomics reveals cell alignment and mitochondrial length change under cyclic stretching in lung cells [J]. Int J Mol Sci, 2020, 21(11): 4074. DOI: 10.3390/ijms21114074.
[12]Lin J, Ou H, Luo B, et al. Capsaicin mitigates ventilator-induced lung injury by suppressing ferroptosis and maintaining mitochondrial redox homeostasis through SIRT3-dependent mechanisms [J]. Mol Med, 2024, 30(1): 148. DOI: 10.1186/s10020-024-00910-y.
[13]Crosas-Molist E, Graziani V, Maiques O, et al. AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration [J]. Nat Commun, 2023, 14(1): 2740. DOI: 10.1038/s41467-023-38292-0.
[14]Dupont S, Wickström SA. Mechanical regulation of chromatin and transcription [J]. Nat Rev Genet, 2022, 23(10): 624-643. DOI: 10.1038/s41576-022-00493-6.
[15]Gruschke S, Gröne K, Heublein M, et al. Proteins at the polypeptide tunnel exit of the yeast mitochondrial ribosome [J]. J Biol Chem, 2010, 285(25): 19022-19028. DOI: 10.1074/jbc.M110.113837.
[16]Krishnamoorthy GP, Davidson NR, Leach SD, et al. EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC [J]. Cancer Discov, 2019, 9(2): 264-281. DOI: 10.1158/2159-8290.CD-18-0606.
[17]Caligiuri G, Tuveson DA. Activated fibroblasts in cancer: Perspectives and challenges [J]. Cancer Cell, 2023, 41(3): 434-449. DOI: 10.1016/j.ccell.2023.02.015
[18]Liu W, Wei H, Gao Z, et al. COL5A1 may contribute the metastasis of lung adenocarcinoma [J]. Gene, 2018, 665: 57-66. DOI: 10.1016/j.gene.2018.04.066.
[19]Zhang H, Dai J, Mu Q, et al. Macrophage heterogeneity and oncogenic mechanisms in lung adenocarcinoma: insights from scRNA-seq analysis and predictive modeling [J]. Front Immunol, 2024, 15: 1491872. DOI: 10.3389/fimmu.2024.1491872.
[20]Alborzian Deh Sheikh A, Akatsu C, Abdu-Allah HHM, et al. The protein tyrosine phosphatase SHP-1 (PTPN6) but not CD45 (PTPRC) is essential for the ligand-mediated regulation of CD22 in BCR-ligated B cells [J]. J Immunol, 2021, 206(11): 2544-2551. DOI: 10.4049/jimmunol.2100109.
鈥�樊庭宇，讲师，E-mail: 526201753@qq.com；宫凤英，副主任医师，E-mail: gfying2011@smu.edu.cn