Ask about this productRelated genes to: SIPA1 Blocking Peptide
- Gene:
- SIPA1 NIH gene
- Name:
- signal-induced proliferation-associated 1
- Previous symbol:
- -
- Synonyms:
- SPA1
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-23
- Date modifiied:
- 2019-04-11
Related products to: SIPA1 Blocking Peptide
Related articles to: SIPA1 Blocking Peptide
- Dysregulation of protein ubiquitination and deubiquitination is a key mechanism driving tumor progression. However, the role of upstream regulators and post-translational mechanisms regulating signal-induced proliferation-associated 1 (SIPA1) stability in colorectal cancer (CRC) remains unclear. This study aimed to investigate novel deubiquitinases that directly bind to and stabilize SIPA1 based on its catalytic activity, along with their underlying action mechanisms. Notably, ubiquitin C-terminal hydrolase L3 (UCHL3) was identified as the novel deubiquitinase. Mechanistically, UCHL3 removed K48-linked polyubiquitin chains from SIPA1 at lysine 805, protecting it from proteasomal degradation. In contrast, the E3 ligase itchy E3 ubiquitin protein ligase (ITCH) promoted SIPA1 ubiquitination and degradation, acting antagonistically to UCHL3. Furthermore, UCHL3 enhanced CRC cell proliferation, invasion, and metastasis through a SIPA1-dependent mechanism. Interestingly, tripartite motif-containing protein 21 regulated UCHL3 post-translationally by targeting UCHL3 for proteasomal degradation. Clinically, UCHL3 and SIPA1 were found to be upregulated in CRC tissues, whereas ITCH was downregulated, with their expression correlating with poor patient prognosis. Altogether, the findings of this study reveal the novel UCHL3-ITCH-SIPA1 regulatory axis that modulates oncogenic signaling and CRC progression, offering new insights into the post-translational regulation of SIPA1 and identifying potential therapeutic targets. - Source: PubMed
Publication date: 2025/12/16
Lou ShenghanWang HaoMo GenshenLi HaoXie HaonanHuang YuzeLi HuiyingMa KeruZhang XinyueYan MeihongZhang JianPi YananHan Peng - Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation. The global rise in the incidence of both AD and cancer suggests a potential link through shared immune-inflammatory pathways. This study aimed to investigate the causal relationship between AD and multiple cancer types and to explore potential underlying biological mechanisms. A two-sample Mendelian randomization (MR) analysis was conducted using data from a genome-wide association study of 6,224 AD patients. Seventeen cancer types were assessed. Additionally, expression quantitative trait loci analysis, pathway enrichment, and survival analyses were performed. MR analysis identified a significant causal relationship between AD and the risk of esophageal cancer (odds ratio [OR] = 0.88, = 0.0247) as well as colorectal cancer (OR = 0.94, = 0.0154). Subsequent research revealed differential expression between tumor and normal tissues, with pathway enrichment highlighting immune processes. No survival association was found in esophageal cancer, but and expression levels could affect outcomes in colorectal cancer. This study provides evidence for a protective causal relationship between AD and the risks of esophageal and colorectal cancers. Immune and inflammatory pathways may mediate this link. - Source: PubMed
Publication date: 2026/02/19
He YangXu AbaiMi XiangbinTang Nina - To investigate the expression of signal-induced proliferation-associated 1 (SIPA1) in colorectal cancer tissues and its relationship with patient prognosis. To explore the effects of SIPA1 on proliferation and migration abilities, as well as the possible molecular mechanisms. Using The Cancer Genome Atlas (TCGA) database to analyze the differential expression of SIPA1 and conduct survival analysis. Then, plotting receiver operating characteristic curve (ROC) and prognosis calibration curve analysis to assess the predictive capability and accuracy of SIPA1 for patient prognosis. Subsequently, verifying the expression levels of SIPA1 in tumor tissues and adjacent normal tissues using immunohistochemistry (IHC) and western blot (WB) assays(from March 1, 2023, to May 1, 2024, pathological specimens of five colorectal cancer patients were selected from the tissue bank of affiliated hospital of Nantong University. tissue microarrays were constructed using both cancerous tissues and adjacent normal tissues), and exploring the correlation between SIPA1 and clinical pathological parameters. Next, establishing SIPA1 stable knockdown cell lines in colorectal cancer cell lines DLD1 and HCT116, and assessing the biological behavior changes of tumor cells after SIPA1 knockdown through cell proliferation, invasion, and migration experiments. Validating the impact of SIPA1 on colorectal cancer cell proliferation through subcutaneous xenograft experiments in nude mice. Exploring the potential pro-tumor mechanisms of SIPA1 through pathway enrichment analysis, and confirming these using WB experiments. The proliferation, invasion and migration of tumor cells were detected after adding PI3K activator. Lastly, conducting correlation analysis between SIPA1 and immune checkpoint, as well as the association with immune cells in the tumor microenvironment. Differential analysis showed that mRNA expression of SIPA1 in colorectal cancer tissues was significantly higher than that in adjacent normal tissues (＜0.05). Prognostic analysis indicated that patients with high expression of SIPA1 had poor overall survival (＜0.001), and the expression level of SIPA1was correlated with lymph node invasion (＜0.001) and N stage (＜0.05). ROC curve and prognosis calibration curve suggest that SIPA1 can effectively predict five-year survival rate of patients (AUC=0.7), and the predictive performance of the model is relatively accurate (＜0.001). WB experiments showed a significant increase in the expression level of SIPA1 protein in colorectal cancer specimens (＜0.001). Immunohistochemistry results indicated higher staining scores of SIPA1 in tumor tissues. experiments demonstrated that SIPA1 knockdown significantly inhibited the proliferation, invasion, and migration capabilities of colorectal cancer cells. In DLD1 and HCT116 cells, the SIPA1-knockdown group exhibited significantly lower absorbance compared to the control group (0.89±0.01 vs. 1.57±0.02 and 0.72±0.01 vs. 1.31±0.03, respectively, both ＜0.001). The SIPA1-knockdown group also demonstrated a reduced number of migrated cells relative to the control group (197.93±16.64 vs. 518.48±29.15 and 171.83±12.49 vs. 446.00±21.81, respectively, both ＜0.001). Furthermore, the cell wound-healing rate was significantly lower in the SIPA1-knockdown group than that in the control group [(0.32±0.01)% vs. (0.61±0.01)% and (0.28±0.01)% vs. (0.75±0.01)%, respectively, both ＜0.001]. animal experiments suggested that SIPA1 knockdown could inhibit tumor growth [(460.35±57.47) mm³ (1 177.55±208.24)mm³, (0.76±0.11)g (1.43±0.08)g, ＜0.05]. Pathway enrichment analysis revealed significant enrichment of the receptor tyrosine kinase signaling pathway, and SIPA1 knockdown could inhibit the activation of the phosphatidylinositide 3-kinases (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3β (GSK3β) signaling pathway. The PI3K activator reversed the inhibitory effect of SIPA1 silencing on tumor cell proliferation, invasion and migration. Correlation analysis indicated that high expression of SIPA1 was associated with immune checkpoints and various immunosuppressive cells (all ＜0.05). SIPA1 is highly expressed in colorectal cancer and associated with poor prognosis. SIPA1 may affect the proliferation and migration abilities of tumor cells by regulating the PI3K/AKT/GSK3β signaling pathway. - Source: PubMed
Wang N ZZhang LChen JChen HWang R CLu C HJi Y F - Sipa1 (signal-induced proliferation-associated gene 1) is known as a specific Rap1 (Ras-related protein 1) GTPase-activating protein that negatively regulates Rap1 signaling. Although Sipa1 has been extensively studied in cancer research, its role in the wound-healing response after myocardial infarction (MI) remains unexplored. - Source: PubMed
Publication date: 2025/06/26
Ko SeienLiu XueyuanTaniguchi YurikaIchihara GenkiKomuro JinYamakawa HiroyukiShirakawa KohsukeHashimoto HisayukiKatsumata YoshinoriEndo JinHattori MasakazuMinato NagahiroSano MotoakiAnzai AtsushiIeda Masaki - Erythrocytosis moderately enhances the oxygen-carrying capacity of the blood and is considered a characteristic response of individuals adapting from low-altitude regions to high-altitude regions. Nevertheless, erythrocytosis can also turn excessive and result in maladaptive syndromes, such as high altitude polycythemia (HAPC). The increased differentiation or proliferation of erythroid cells in the bone marrow may be a crucial factor leading to accumulation of peripheral erythroid cells. However, the mechanism of erythroid regulation within the bone marrow of high-altitude erythrocytosis remains insufficiently systematically observed. We utilized single-cell transcription sequencing to characterize bone marrow cells following chronic hypoxic exposure and found that bone marrow erythrocytosis is associated with the accumulation of Baso-E, Poly-E, and Ortho-E cells at the terminal stage of erythroid lineage differentiation. Through analysis of differential gene expression and localization in differentiated cells within the erythroid lineage, we confirmed that DDIT4 expression was localized in advanced differentiated erythroblast including Baso-E, Poly-E and Ortho-E, its expression was significantly enhanced by hypoxia exposure. We demonstrated that overexpression of DDIT4 could promote K562 cell differentiation, and through the IP pull-down interaction protein profile, we found that DDIT4 might participate in regulating the cell cycle by interacting with SIPA1 to promote the proliferation of erythroid cells and may be involved in HAPC. - Source: PubMed
Publication date: 2024/10/31
Cui YuZhou Xiao-YinLi Xiao-XuYang Yi-DongYang Cheng-ZhongChen De-WeiHuang JianGao Yu-Qi