SP1 (Sp1 Transcription Factor)

ECRG4 inhibits breast cancer progression by positively regulating NFIC/PTEN to suppress the SHP2/PI3K/SP1 signaling pathway. Targeting this signaling axis may provide a new strategy for breast cancer treatment.

Overall, our findings identify SP1 as a central negative regulator of ADAMTS-1 and ADAMTS-8, contributing to tumor progression in CRC and osteosarcoma. The SP1-ADAMTS axis represents a potentially important molecular network in cancer biology and may provide a basis for developing novel biomarkers or targeted therapeutic strategies.

Moreover, both promoter and ChIP analysis indicated that NR4A1 and NR4A2 acted as ligand-dependent cofactors of Sp1/4-mediated expression of CD71 in TNBC cells. Thus, CD71, a key biomarker of ferroptosis is an NR4A1/2/Sp regulated gene that can be directly targeted by DIM-3,5 inverse NR4A1/2 agonists to induce ferroptosis in TNBC cells.

Conclusions. For the SP1 gene, the above hypothesis is supported by our analysis of open-access data on gene expression in patients with the aforementioned diagnoses and fits a probable mechanism of the "HD-LC" dystropy.

The findings suggest that SP1 is a critical regulator of PDAC initiation and progression through its control of metabolic remodeling. Targeting SP1 and PFKFB4 represents a promising therapeutic strategy for PDAC treatment.

SP1 overexpression induced EMT and repressed metastatic colonization of PCa CTCs. Thus, the induction of EMT in CTCs by SP1 augmentation may hold promise as a novel treatment for PCa by staving off metastasis.

SP1-activated CLEC7A could facilitate OSCC cell malignant behaviors and M2 macrophage polarization, providing a possible therapeutic target for OSCC treatment. The online version contains supplementary material available at 10.1007/s10616-025-00787-7.

BAP1 promotes bladder cancer progression by inhibiting the ubiquitination of SP1, YAP, and PD-L1 and activating the CAS6/AXL signaling pathway. These findings highlight BAP1 as a potential therapeutic target for bladder cancer treatment.

Moreover, both promoter and ChIP analysis indicated that NR4A1 and NR4A2 acted as ligand-dependent cofactors of Sp1/4-mediated expression of CD71 in TNBC cells. CD71, a key biomarker of ferroptosis is an NR4A1/2/Sp regulated gene that can be directly targeted by DIM-3,5 inverse NR4A1/2 agonists to induce ferroptosis in TNBC cells.

In addition, EphA7 demethylation reduced the half-maximal inhibitory concentration (IC50) of cisplatin and paclitaxel. Pooled analysis revealed that EphA7 promoter hypermethylation was positively correlated with tumor purity but negatively correlated with immune cell infiltration, cytotoxic T lymphocyte (CTL) and immune checkpoint (IC) activity, and the expression of EphA7 was significantly positively correlated with tumor mutational burden (TMB), microsatellite instability (MSI) and the presence of single nucleotide variant (SNV) neoantigens, suggesting a better prognosis for patients with EphA7 promoter hypomethylation and high expression. Collectively, these findings indicate that targeted demethylation of the EphA7 promoter and restoration of endogenous EphA7 expression by dCas9-Tet1 are promising therapeutic approaches and are favorable for the prognosis of CC patients.

These findings suggest a novel role for PPP3CB in preventing PDAC progression by promoting ATOH8 nuclear translocation and transcriptionally inhibiting Sp1. Consequently, PPP3CB emerges as a potential therapeutic target for PDAC.

These studies reveal a novel feedforward lncRNA circuit contributing to pulmonary carcinogenesis and suggest that pharmacologic targeting of SP1 and/or NFĸB may be useful strategies for restoring ZNFX1 expression for lung tumor therapy.