SIX1 (SIX Homeobox 1)

ISL1 serves as both a predictive biomarker and functional dependency, as evidenced by essentiality for cell survival and loss following treatment. Prospective studies using ISL1 as a predictive biomarker for lurbinectedin are planned.

Genetic ablation of SIX1 and pharmacological disruption of the SIX1/EYA1 interaction impair AML maintenance and resensitize cells to DNA-damaging therapies. These findings establish RDGN as a promising therapeutic target in AML and potentially in solid tumors marked by SIX1/RDGN re-expression.

One signature distinguished neuroblastoma samples with sensitivity to navitoclax, a BCL2 family inhibitor...The combination of multiomics analysis and drug sensitivity profiling identified two signatures related to drug sensitivity in pediatric solid tumors, contributing to the advancement of functional precision medicine and personalized treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

Additionally, NCYM facilitated tumor growth and formation of lung metastasis in vivo. In summary, the exogenous overexpression of NCYM could play a critical role in WT progression by mediating SIX1 and β-catenin as an oncopromoting factor.

The expression of Six1 was reduced in type II alveolar epithelial cells (AECII) in both patients with IPF and mouse models of PF induced by bleomycin (BLM)...These findings suggest that Six1 is a contributor to the progression of IPF by regulating AECII senescence, emphasizing the therapeutic potential of targeting Six1 to alleviate PF. This study underscores the necessity of exploring Six1 inhibitors further as promising candidates for treating IPF.

In addition, this study found a new cell interaction model, in which the above-mentioned secreted IL6 can promote the activation of STAT3 signaling pathway, EMT and stemness transformation in the surrounding cells with low expression of SIX1 in a paracrine manner. Our data favored that SIX1/ZEB1/IL6 axis activated the STAT3 signaling pathway of the breast cells themselves and surrounding cells with low SIX1 expression, thus promoting EMT and stemness transformation, activating the malignant progression of the whole breast cancer.

The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC. This combination enhances the expression of VEGFc, facilitates the invasion of GC cells, and may be linked to inhibitory immune cells and the tumor immune microenvironment.

These results suggest that SIX1 regulates proliferation and glucose metabolism in cervical cancer cells by promoting the transcription of key glycolytic enzymes, such as ENO1. Understanding this regulatory mechanism is crucial for identifying potential therapeutic targets for cervical cancer.

These findings indicate that KP-10 plays a crucial role in suppressing EC progression and represents a promising therapeutic target for clinical treatment. However, more comprehensive studies are needed to fully elucidate the underlying mechanisms and explore the clinical potential of KP-10 in EC therapy.

This review aims to enhance our understanding of the function and significance of Six1 in cancers while providing a valuable reference for Six1-based cancer diagnosis, prognosis, and therapeutic interventions. This knowledge will facilitate more in-depth oncology research related to Six1, particularly in identifying drug resistance mechanisms and developing precision-targeted therapies.

The findings of this study indicate that SIX1 expression is a marker of poor prognosis in PTC, suggesting that its high expression is linked with more aggressive tumor characteristics and advanced disease stages. Importantly, the impact of SIX1 expression varies between C-PTC and FV-PTC, predicting distinct prognostic factors in each subtype. This suggests that SIX1 could be utilized not only as a prognostic biomarker but also in developing subtype-specific therapeutic strategies for PTC patients.

Moreover, the expression of GPT2 is upregulated and strongly correlated with the expression of Ku70/SIX1 in PC tissues. In summary, our findings not only provide insight into the mechanistic interactions between Ku70 and SIX1, but also highlight the significance of the Ku70-SIX1-GPT2 axis for α-KG metabolism and PC carcinogenesis.