Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer

Zhang, Huikun; Guo, Zhifang; Liu, Xiaoli; Zhao, Yawen; Chen, Yongzi; Zhang, Ming; Fu, Li; Gu, Feng; Ma, Yihui

doi:10.1038/s41419-021-04218-1

Cited by 4 publications

(1 citation statement)

References 45 publications

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“…www.nature.com/scientificreports/ Moreover, the GO and KEGG enrichment analysis found that the DNA replication, glucose metabolic process, and glycolysis pathways were the most enriched in the pathways related to IL score. Studies have discovered that cancer is correlated with errors that occur during DNA replication 50 , and the inhibition of DNA replication is shown to be beneficial to improve the prognosis of BRCA 51 . Recent research has demonstrated the crucial role played by glucose metabolic process in the growth of TNBC 52 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive evaluation of breast cancer immunotherapy and tumor microenvironment characterization based on interleukin genes-related risk model

Bai

Wang³

et al. 2022

Sci Rep

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Breast cancer (BRCA) is the most prevalent malignancy and the leading cause of death in women. Interleukin (IL) genes are critical in tumor initiation and control. Nevertheless, the prognosis value of the IL in BRCA remains unclear. We collected data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and 94 IL genes were identified from GeneCard. Based on the random forest (RF), least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox regression analysis, we constructed an IL signature. GSE22219, GSE25065, and GSE21653 were derived as validation sets. The expression differences in the tumor microenvironment (TME), immunotherapy, and chemosensitivity of BRCA between the high- and low-risk groups were evaluated. Overall, 21 IL genes were selected to construct an IL risk model, of which IL18BP, IL17D, and IL23A were the first time identified as prognostic genes in BRCA. IL score could distinguish BRCA patients with inferior outcomes, and AUC of it was 0.70, 0.76, and 0.72 for 1-,3- and 5- years, respectively, which was also verified in GSE22219, GSE25065, and GSE21653 cohorts. Meanwhile, compared to luminal A and luminal B, HER2-positive and TNBC had significantly higher IL score. Besides, the high-risk group had a significantly higher prevalence of TP53 and TTN but a lower prevalence of PIK3CA, as well as higher tumor mutation burden (TMB) and neoantigen level. High- and low-risk groups exhibited notable differences in immunomodulators and tumor infiltrates immune cells (TIICs), and the high-risk group had significantly lower Tumor Immune Dysfunction and Exclusion (TIDE) score. Additionally, the high-risk group has more responders to immune or anti-HER2 combination therapy, whereas the low-risk group has higher sensitivity to docetaxel and paclitaxel. Consequently, we constructed a reliable risk model based on the IL genes, which can provide more information on both the risk stratification and personalizing management strategies for BRCA.

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Section: Discussionmentioning

confidence: 99%

Comprehensive evaluation of breast cancer immunotherapy and tumor microenvironment characterization based on interleukin genes-related risk model

Bai

Wang³

et al. 2022

Sci Rep

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Advancements and challenges of R-loops in cancers: Biological insights and future directions

Li,

Shao,

et al. 2025

Cancer Letters

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Intersectin — many facets of a scaffold protein

Mintoo,

Rajagopalan,

O'Bryan

2024

Biochemical Society Transactions

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Intersectin (ITSN) is a multi-domain scaffold protein with a diverse array of functions including regulation of endocytosis, vesicle transport, and activation of various signal transduction pathways. There are two ITSN genes located on chromosomes 21 and 2 encoding for proteins ITSN1 and ITSN2, respectively. Each ITSN gene encodes two major isoforms, ITSN-Long (ITSN-L) and ITSN-Short (ITSN-S), due to alternative splicing. ITSN1 and 2, collectively referred to as ITSN, are implicated in many physiological and pathological processes, such as neuronal maintenance, actin cytoskeletal rearrangement, and tumor progression. ITSN is mis-regulated in many tumors, such as breast, lung, neuroblastomas, and gliomas. Altered expression of ITSN is also found in several neurodegenerative diseases, such as Down Syndrome and Alzheimer's disease. This review summarizes recent studies on ITSN and provides an overview of the function of this important family of scaffold proteins in various biological processes.

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Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer

Cited by 4 publications

References 45 publications

Comprehensive evaluation of breast cancer immunotherapy and tumor microenvironment characterization based on interleukin genes-related risk model

Comprehensive evaluation of breast cancer immunotherapy and tumor microenvironment characterization based on interleukin genes-related risk model

Advancements and challenges of R-loops in cancers: Biological insights and future directions

Intersectin — many facets of a scaffold protein

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