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Review Open Access

Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review)

  • Authors:
    • Kaiwei Wang
    • Yaoqi Li
    • Zhening Guo
    • Lin Song
    • Xiaoliang Ding
    • Linsheng Liu
    • Tao Hu
    • Yicong Bian
    • Chenrong Huang
    • Liyan Miao
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 19
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    Published online on: November 18, 2025
       https://doi.org/10.3892/or.2025.9024
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Abstract

Non‑small cell lung cancer (NSCLC), accounting for >85% of LC cases, remains a therapeutic challenge due to its low 5‑year survival rate, tumor heterogeneity and drug resistance. The SRY‑related high‑mobility group‑box (SOX) family comprises transcription factors involved in the initiation and progression of NSCLC. These factors regulate epithelial‑mesenchymal transition and angiogenesis, interact with epidermal growth factor receptor/KRAS pathways to influence tumor invasion and promote chemotherapy resistance by sustaining tumor stemness. The present review aimed to summarize the expression patterns, molecular mechanisms and clinical relevance of SOX family members (such as SOX2, SOX4 and SOX9) in NSCLC, as well as their potential as diagnostic biomarkers and therapeutic targets, and the application of emerging technology in elucidating their functions. The present review aimed to provide a theoretical foundation for precision diagnostics and therapeutics to foster more effective NSCLC treatment.
View Figures

Figure 1

Classification and structure of the
SOX family in non-small cell lung cancer. (A) Classification of the
SOX family in non-small cell lung cancer. (B) Structure of SOX
family. HMG, high mobility group; TAD, transactivation domain; GRD,
Glycine-Rich domain; CC, Coiled-coil domain; DD, dimerization
domain; PQA, Proline-Glutamine-Alanine-rich domain; aa, amino
acid.

Figure 2

Members of the SOX family exhibit
functional diversity in the occurrence and development of non-small
cell lung cancer. Certain members can affect the proliferation,
apoptosis, invasion and metastasis abilities of tumor cells by
regulating key signaling pathways, thereby exerting
tumor-suppressing or -promoting effects.

Figure 3

Members of the SOX family play
important roles in multiple biological processes such as cell
proliferation, apoptosis, migration, stem maintenance and drug
tolerance of NSCLC by interacting with key signaling pathways such
as Wnt/β-catenin, TGF-β and EGFR. The abnormal regulation of these
signaling pathways not only affects the basic behavioral
characteristics of tumor cells, but may also lead to changes in the
response of NSCLC to treatment and disease progression. NSCLC,
non-small cell lung cancer; LRP, low-density lipoprotein
receptor-related protein; ABCC, ATP-binding cassette, sub-family C;
SARA, Smad-anchor for receptor activation; GSK, glycogen synthase
kinase; CKI, Casein Kinase I; ZEB, Zinc Finger E-Box Binding
Homeobox; EMT, Epithelial-Mesenchymal Transition; IC, Intracellular
Domain.
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Copy and paste a formatted citation
Spandidos Publications style
Wang K, Li Y, Guo Z, Song L, Ding X, Liu L, Hu T, Bian Y, Huang C, Miao L, Miao L, et al: Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review). Oncol Rep 55: 19, 2026.
APA
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L. ... Miao, L. (2026). Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review). Oncology Reports, 55, 19. https://doi.org/10.3892/or.2025.9024
MLA
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L., Hu, T., Bian, Y., Huang, C., Miao, L."Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review)". Oncology Reports 55.1 (2026): 19.
Chicago
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L., Hu, T., Bian, Y., Huang, C., Miao, L."Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review)". Oncology Reports 55, no. 1 (2026): 19. https://doi.org/10.3892/or.2025.9024
Copy and paste a formatted citation
x
Spandidos Publications style
Wang K, Li Y, Guo Z, Song L, Ding X, Liu L, Hu T, Bian Y, Huang C, Miao L, Miao L, et al: Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review). Oncol Rep 55: 19, 2026.
APA
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L. ... Miao, L. (2026). Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review). Oncology Reports, 55, 19. https://doi.org/10.3892/or.2025.9024
MLA
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L., Hu, T., Bian, Y., Huang, C., Miao, L."Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review)". Oncology Reports 55.1 (2026): 19.
Chicago
Wang, K., Li, Y., Guo, Z., Song, L., Ding, X., Liu, L., Hu, T., Bian, Y., Huang, C., Miao, L."Role of the SOX family in non‑small cell lung cancer: Molecular mechanisms and therapeutic implications (Review)". Oncology Reports 55, no. 1 (2026): 19. https://doi.org/10.3892/or.2025.9024
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