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Review Open Access

Function of SP1 in tumors and focused treatment approaches for immune evasion (Review)

  • Authors:
    • Xin Wang
    • Pingping Cui
    • Yongqi Deng
    • Baohua Zhang
    • Zhihui Gao
    • Tangyue Li
    • Yingchun Yin
    • Jing Li
  • View Affiliations / Copyright

    Affiliations: School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China, Peking University Health Science Center, Peking University First Hospital, Xicheng, Beijing 100034, P.R. China, Department of Pathology, Zibo Central Hospital, Zibo, Shandong 255020, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 483
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    Published online on: August 14, 2025
       https://doi.org/10.3892/ol.2025.15230
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Abstract

Immune escape is a phenomenon in which tumor cells or infections evade detection and clearance by the host immune system in various ways. During an antitumor immune response, cells increase the concentration of pentameric stalk, which enhances antigen presentation and recognition by the immune system. It has been found that both increased and decreased levels of specificity protein 1 (SP1) control oncogenes, thereby influencing tumorigenesis and cancer development. Thus, elucidating the mechanism underlying the role of SP1 in tumors may help identify novel prognostic indicators. However, the immune escape mechanism involved in SP1 poses new challenges to diagnosis and treatment. The present review used a combination of analogies and summaries to explore the structure, function, regulatory mechanism and biological activity of SP1 in normal and cancer cells, and aimed to discuss the regulatory function of SP1 in different tumors, as well as the relevant association between SP1 and clinical diagnosis and treatment, which revealed the importance of SP1 in tumorigenesis and cancer development. The novelty of the present review lies in the identification of novel immune evasion mechanisms and immunotherapeutic techniques that provide new insights and approaches for a deeper understanding of the role of SP1 in malignant tumors. 
View Figures

Figure 1

Schematic representation of SP1
structure. The diagram outlines the distinct domains of SP1,
including the N-terminal domain (aa 1–145), transactivation domain
A (TAD A; aa 146–251), transactivation domain B (TAD B; aa
261–495), charged domain (aa 496–610), DNA binding domain (aa
642–708) and domain D (aa 708–785). The N-terminal domain is marked
as inhibitory, while TAD A and TAD B are highlighted with color
coding to indicate regions rich in serine/threonine (light orange)
and glutamic acid (yellow). The charged domain is represented with
a series of positive charges (+) and a series of negative charges
(−). The DNA-binding domain (aa 642–785) comprises two zinc finger
motifs (Zn, aa 642–708) followed by domain D (aa 708–785), which
collectively mediate GC-box recognition. Figure was created using
Adobe Illustrator version 28.0 (Adobe, Inc.). Numbers indicate aa
positions. aa, amino acid; Btd, buttonhead; SP1, specificity
protein 1; TAD, tight adherence.

Figure 2

Regulatory mechanism of SP1 in
neuronal injury. Schematic diagram illustrates the interaction
between the BBB and neuronal damage. The influx of SP1, a
transcription factor, affects neuronal integrity. SP1
interacts with FOXM1, promoting the expression of SNAI2 and CXCL12,
which are associated with neuronal damage. Additionally, SP1
modulates CDK9 activity, further contributing to neuronal
impairment. This diagram highlights the molecular pathways involved
in the disruption of the BBB and subsequent neuronal damage,
providing insights into potential therapeutic targets for
neuroprotection. Figure was created using Adobe Illustrator version
28.0 (Adobe, Inc.). CDK9, cyclin dependent kinase 9; CXCL12, C-X-C
motif chemokine ligand 12; FOXM1, forkhead box M1; SNAI2, Snail
family transcriptional repressor 2; SP1, specificity protein
1; BBB, blood-brain barrier.

Figure 3

Key molecules and pathways regulated
by SP1 in tumorigenesis and cancer progression. The key
molecules and pathways annotated in this figure demonstrate the
pleiotropic roles of SP1 in tumorigenesis and cancer
progression, highlighting its potential as a therapeutic target.
Figure was created using Adobe Illustrator version 28.0 (Adobe,
Inc.). NF-κB, nuclear factor κB; PTEN, phosphatase and tensin
homolog; SNHG7, small nucleolar RNA host gene 7; SP1,
specificity protein 1; TUG1, taurine-upregulated gene 1; miR,
microRNA; LINC00659; long intergenic non-protein coding RNA 659;
AKT, protein kinase B; mTOR, mTOR, mechanistic target of rapamycin;
CDK1, cyclin dependent kinase; FLT1, fms-related tyrosine kinase 1
.

Figure 4

Regulatory mechanism of SP1 in
gastric cancer. SP1, a transcription factor, interacts with
various molecules and pathways that promote cancer cell
proliferation, migration and invasion. Specifically, SP1
influences the expression of lncRNA, miR-527, miR-00659 and
circular RNA LINC00659, which in turn regulate the activity of
downstream targets such as AQP370, OSMR, VEGFA and P62. These
targets are associated with tumor growth, migration, invasion and
autophagy. The diagram includes a legend identifying various cell
types involved in the tumor microenvironment, including gastric
cancer cells, cancer-associated fibroblasts, CD8+ T cells,
macrophages, extracellular matrix components and gastric mucosal
cells. Figure was created using Adobe Illustrator version 28.0
(Adobe, Inc.). LINC00659, long intergenic non-protein coding RNA
659; lncRNA, long noncoding RNA; OSMR, oncostatin M receptor;
SP1, specificity protein 1; TNM, tumor-node-metastasis;
VEGFA, vascular endothelial growth factor A; miR, microRNA; HOOK,
hook microtubule tethering protein; AQP3, aquaporin3.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Cui P, Deng Y, Zhang B, Gao Z, Li T, Yin Y and Li J: Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review). Oncol Lett 30: 483, 2025.
APA
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T. ... Li, J. (2025). Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review). Oncology Letters, 30, 483. https://doi.org/10.3892/ol.2025.15230
MLA
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T., Yin, Y., Li, J."Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review)". Oncology Letters 30.4 (2025): 483.
Chicago
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T., Yin, Y., Li, J."Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review)". Oncology Letters 30, no. 4 (2025): 483. https://doi.org/10.3892/ol.2025.15230
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Cui P, Deng Y, Zhang B, Gao Z, Li T, Yin Y and Li J: Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review). Oncol Lett 30: 483, 2025.
APA
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T. ... Li, J. (2025). Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review). Oncology Letters, 30, 483. https://doi.org/10.3892/ol.2025.15230
MLA
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T., Yin, Y., Li, J."Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review)". Oncology Letters 30.4 (2025): 483.
Chicago
Wang, X., Cui, P., Deng, Y., Zhang, B., Gao, Z., Li, T., Yin, Y., Li, J."Function of <em>SP1</em> in tumors and focused treatment approaches for immune evasion (Review)". Oncology Letters 30, no. 4 (2025): 483. https://doi.org/10.3892/ol.2025.15230
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