EWI2 promotes endolysosome-mediated turnover of growth factor receptors and integrins to suppress lung cancer

Wang, Jie; Wren, Jonathan D.; Ding, Yongjie; Chen, Junxiong; Mittal, Nikhil; Xu, Chao; Li, Xing; Zeng, Cengxi; Wang, Meng; Shi, Jing; Zhang, Yanhui H.; Han, Sangyoon J.; Zhang, Xin A.

doi:10.1016/j.canlet.2022.215641

Cited by 5 publications

(1 citation statement)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the era of single-cell sequencing, the significance of the integrin superfamily genes in complex cellular communication within the tumor microenvironment has been rediscovered. Integrin superfamily genes play an important role in cancer (Miyamoto et al 2022 ; Wang et al 2022 ), influencing various cancer-related processes including tumor initiation, microenvironment modifications, cell migration, tumor–stroma interactions, fibroblast activation, colonization, immune dysfunction, and drug resistance (Cooper and Giancotti 2019 ; Kanchanawong and Calderwood 2023 ; Margadant and Sonnenberg 2010 ; Mu et al 2002 ; Nan et al 2022 ; Sheta et al 2021 ; Slack et al 2022 ). However, the association between genome alteration of integrins and treatment resistance remains unclear.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis

Zheng

et al. 2023

Funct Integr Genomics

View full text Add to dashboard Cite

Contribution of integrin superfamily genes to treatment resistance remains uncertain. Genome patterns of thirty integrin superfamily genes were analyzed of using bulk and single-cell RNA sequencing, mutation, copy number, methylation, clinical information, immune cell infiltration, and drug sensitivity data. To select the integrins that are most strongly associated with treatment resistance in pancreatic cancer, a purity-independent RNA regulation network including integrins were constructed using machine learning. The integrin superfamily genes exhibit extensive dysregulated expression, genome alterations, epigenetic modifications, immune cell infiltration, and drug sensitivity, as evidenced by multi-omics data. However, their heterogeneity varies among different cancers. After constructing a three-gene (TMEM80, EIF4EBP1, and ITGA3) purity-independent Cox regression model using machine learning, ITGA3 was identified as a critical integrin subunit gene in pancreatic cancer. ITGA3 is involved in the molecular transformation from the classical to the basal subtype in pancreatic cancer. Elevated ITGA3 expression correlated with a malignant phenotype characterized by higher PD-L1 expression and reduced CD8+ T cell infiltration, resulting in unfavorable outcomes in patients receiving either chemotherapy or immunotherapy. Our findings suggest that ITGA3 is an important integrin in pancreatic cancer, contributing to chemotherapy resistance and immune checkpoint blockade therapy resistance. Graphical abstract

show abstract