Ask about this productRelated genes to: SIX1 antibody
- Gene:
- SIX1 NIH gene
- Name:
- SIX homeobox 1
- Previous symbol:
- DFNA23
- Synonyms:
- -
- Chromosome:
- 14q23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-09-29
- Date modifiied:
- 2015-09-02
Related products to: SIX1 antibody
Related articles to: SIX1 antibody
- Lactylation, a lactate-dependent posttranslational modification, is involved in cancer development. Here, we showed that GCN5L2 physically interacts with nuclear SIX1 and acts as a key regulator of SIX1 lactylation. GCN5L2 depletion promotes APC/Cdh1 binding to SIX1, increases SIX1 ubiquitination, and reduces SIX1 protein stability. Functionally, the GCN5L2-SIX1 axis promotes glucose uptake, glycolysis process, and energy supply in TNBC cells. GCN5L2 knockdown attenuates the growth and migration of TNBC cells, and increases the sensitivity of TNBC cells to paclitaxel. Overexpression of SIX1 reverses the GCN5L2 knockdown-induced glycolysis and growth suppression in TNBC cells. In addition, GCN5L2 expression is enriched and positively correlated with SIX1 in clinical TNBC tissues. More importantly, we demonstrated 9‴-Methyl salvianolate B as a candidate modulator of the GCN5L2-SIX1 complex via an unbiased screening. 9‴-Methyl salvianolate B suppresses the GCN5L2-SIX1 axis and blocks the glycolysis, proliferation, metastasis, and paclitaxel resistance of TNBC cells. Overall, this study highlights the significance of the GCN5L2-SIX1 axis in sustaining glycolysis and TNBC development, and provides experimental evidence of 9‴-Methyl salvianolate B as a candidate modulator of the GCN5L2-SIX1 axis, presenting a promising strategy for TNBC management. - Source: PubMed
Publication date: 2026/08/14
Liao YuningYin ShushaPeng E-YingWu JinjieYao YuHe WanyingHuang HongbiaoLiu QingDeng YuanfeiYao LeyiCai Gengxi - Cervical cancer aggressiveness and therapeutic resistance are driven by metabolic reprogramming and redox imbalance. Within this context, NAD(P)H: quinone oxidoreductase 1 (NQO1), a critical regulator of cellular redox homeostasis and energy metabolism, is highly expressed in several types of cancer and is associated with poor prognosis; however, its role in cervical cancer remains unclear. This study demonstrates that NQO1 is significantly upregulated in cervical cancer, promoting proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Mechanistically, NQO1 suppresses AMP-activated protein kinase (AMPK) phosphorylation to reduce reactive oxygen species (ROS), while stabilizing HIF1α by preventing its proteasomal degradation. Consequently, stabilized HIF1α upregulates sine oculis homeobox 1 (SIX1) to enhance glycolytic enzyme transcription, driving aerobic glycolysis. Functional rescue experiments demonstrated that knockdown of NQO1, HIF1α, or SIX1 significantly inhibited glycolytic flux, tumor growth, and metastasis . Thus, the NQO1/HIF1α-SIX1 axis orchestrates metabolic reprogramming and EMT to promote cervical cancer progression and is a promising therapeutic target. - Source: PubMed
Publication date: 2026/07/30
Zhu GuangPiao ZhenggenGao YuanCong XianlingWei PengchengHan AnnaZhou HoukunLin ZhenhuaJin Toufeng - The mammalian auditory sensory epithelium consists of hair cells (HCs), whose stereociliary bundles convert sound-evoked vibrations into electrical signals, and supporting cells (SCs), which provide mechanical stability. The transcription factor SIX1 is essential during otic neurosensory cell specification and HC commitment, but its contribution after birth has remained elusive. Here, we show that SIX1 is required for maintaining the structure and function of the adult cochlear sensory epithelium. Conditional deletion of in SCs or HCs of young adult mice causes profound deafness. SC-specific deletion disrupts epithelial organization and promotes SC loss with secondary HC degeneration, whereas HC-specific loss results in stereociliary-bundle defects and progressive HC death. To define early molecular defects, we performed single-nucleus RNA-seq before widespread degeneration and found early collapse of mature HC identity and functional gene programs, including mechanotransduction, stereociliary-bundle, and synaptic networks. SIX1 ChIP-seq analysis in the mature cochleamapped SIX1 occupancy at regulatory elements near genes involved in epithelial junctions, actin/cytoskeletal regulation, ion transport, mechanotransduction, and cell survival, and overlapped with a subset of -dependent transcripts and deafness loci. Together, these results identify SIX1 as a key transcriptional regulator of adult cochlear homeostasis and reveal downstream gene networks that preserve sensory epithelial integrity and hearing throughout life. - Source: PubMed
Publication date: 2026/08/03
Ma XiaohuiAsamiya IanLouie ElizabethChen YingLi AiqunXu Pin-Xian - Non-small cell lung cancer (NSCLC) exhibits stem-like characteristics that drive tumor aggressiveness and treatment resistance. The molecular chaperone Glucose-Regulated Protein 78 (GRP78) is substantially elevated in NSCLC compared to normal tissues and cell lines. In clinical samples, GRP78 protein levels correlated with advanced tumor stage and lymph node metastasis. Pharmacological inhibition of GRP78 using BAPTA-AM and GRP78-IN-3 significantly suppressed NSCLC cell viability while promoting apoptosis. The inhibitors effectively attenuated cell migration by downregulating matrix metalloproteinases and reversed epithelial-mesenchymal transition by modulating key cadherin expression profiles. Importantly, GRP78 inhibition substantially reduced cancer stem cell markers and impaired spheroid formation capability. Genetic knockdown of GRP78 in A549 and H1975 cells recapitulated the effects of pharmacological inhibition, reducing cell migration, reversing EMT, attenuating stemness, and suppressing β-catenin signaling. Conversely, GRP78 overexpression in A549 and H1975 cells induced opposite effects, promoting mesenchymal markers, enhancing stemness proteins, and increasing spheroid size. Mechanistic studies revealed that this anti-tumor activity operates through suppression of β-catenin signaling mediated by SIX1, as evidenced by SIX1-overexpression rescue experiments. These findings demonstrate that GRP78 acts as a key regulator of NSCLC stemness and metastatic potential by coordinating epithelial plasticity and stemness pathways, positioning it as a promising therapeutic target for NSCLC treatment. - Source: PubMed
Tong GuopingQi Huanyu - Wilms' tumor (WT) is the most common primary renal malignancy in children and it is a paradigmatic developmental kidney tumor arising from disrupted nephrogenesis. Classically framed as a developmental disorder of the nephron progenitor compartment, WT also exhibits clinically relevant endocrine features, most notably renin-mediated hypertension and, less commonly, selected paraneoplastic syndromes including Cushing syndrome, erythrocytosis, hypercalcemia, and acquired von Willebrand disease. Biochemically, atypical elevations of α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-HCG) may complicate the differential diagnosis of pediatric renal and retroperitoneal masses. At the molecular level, hormone-linked pathways-including the insulin-like growth factor (IGF) axis, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β)/Smad signaling, the renin-angiotensin system (RAS) and the WT1-centered gonadal-adrenal axis-converge on core processes that drive WT growth, angiogenesis, epithelial-mesenchymal transition (EMT) and microenvironmental remodeling. These pathways intersect with a heterogeneous genetic and epigenetic landscape dominated by alterations in WT1, 11p15/WT2, SIX1/2, WDR4 and dysregulated non-coding RNAs. In this narrative review, we first outline the clinical and diagnostic landscape of WT, and then summarize endocrine and paraneoplastic manifestations. We next dissect the main hormone-related signaling pathways and their genetic underpinnings, and discuss how these insights may inform risk stratification, supportive management, and future therapy, ranging from blood pressure control with RAS blockade to limited anti-VEGF exploration and more speculative IGF-axis and TGF-β-targeted interventions. Clinically, the endocrine interface of WT is narrow but important: renin-mediated hypertension and selected diagnostic dilemmas are directly actionable, whereas rare paraneoplastic syndromes are mainly case-based observations and most endocrine-related therapeutic pathways remain investigational. This evidence-stratified perspective may help align developmental biology with practical clinical decision-making. - Source: PubMed
Publication date: 2026/07/21
Zhanghuang ChenghaoYang ZhaoYao GuipingLi QiurongZhang DeweiYao ZhigangJi FengmingYan Bing