A Regulatory Axis between Epithelial Splicing Regulatory Proteins and Estrogen Receptor α Modulates the Alternative Transcriptome of Luminal Breast Cancer

Elhasnaoui, Jamal; Ferrero, Giulio; Miano, Valentina; Franchitti, Lorenzo; Tarulli, Isabella; Tarrero, Lucia Coscujuela; Cutrupi, Santina; Bortoli, Michele De

doi:10.3390/ijms23147835

Cited by 6 publications

(3 citation statements)

References 71 publications

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“…TOP1 is a metalloendopeptidase, it hydrolyzes neuroendocrine and cardiovascular peptides [47], and may affect angiotensin converting enzyme II (ACEII) expression in alveolar epithelial cells and vascular endothelial cells that is associated with alveolar fluid clearance [47]. ESRP2 is an RNA binding proteins that controls splicing events during epithelial-mesenchymal transition [48] and is required for maintenance of epithelial cell barriers [49] and lung cell homeostasis [50]. IFT88, a subunit of proteins in the IFT machinery.…”

Section: Plos Onementioning

confidence: 99%

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease

Sakarin,

Rungsipipat,

Roytrakul

et al. 2024

PLoS ONE

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In dogs with degenerative mitral valve disease (DMVD), pulmonary hypertension (PH) is a common complication characterized by abnormally elevated pulmonary arterial pressure (PAP). Pulmonary arterial remodeling is the histopathological changes of pulmonary artery that has been recognized in PH. The underlying mechanisms that cause this arterial remodeling are poorly understood. This study aimed to perform shotgun proteomics to investigate changes in protein expression in pulmonary arteries and lung tissues of DMVD dogs with PH compared to normal control dogs and DMVD dogs without PH. Tissue samples were collected from the carcasses of 22 small-sized breed dogs and divided into three groups: control (n = 7), DMVD (n = 7) and DMVD+PH groups (n = 8). Differentially expressed proteins were identified, and top three upregulated and downregulated proteins in the pulmonary arteries of DMVD dogs with PH including SIK family kinase 3 (SIK3), Collagen type I alpha 1 chain (COL1A1), Transforming growth factor alpha (TGF-α), Apoptosis associated tyrosine kinase (AATYK), Hepatocyte growth factor activator (HGFA) and Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) were chosen. Results showed that some of the identified proteins may play a role in the pathogenesis of pulmonary arterial remodeling. This study concluded shotgun proteomics has potential as a tool for exploring candidate proteins associated with the pathogenesis of PH secondary to DMVD in dogs.

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Section: Plos Onementioning

confidence: 99%

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease

Sakarin,

Rungsipipat,

Roytrakul

et al. 2024

PLoS ONE

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“…Higher levels of ESRP1 expression have been detected in breast cancer, and have been associated with poor prognosis in oestrogen receptor positive breast cancer cells [54]. ESRP1 is controlled by the steroid hormone receptor ERα in breast cancer cells, and there are ERα binding sites within ESRP1 and ESRP2 promoters [55]. ESRP1 is also controlled by the transcription factor E2F1 in breast cancer cells and sensitive to oxygen levels [56].…”

Section: Could Esrp1 and Esrp2 Be Lineage Survival Oncogenes In Other...mentioning

confidence: 99%

Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer

Elliott

2024

Preprint

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Prostate cancer progression is connected to the activity of conventional oncogenes and tumour suppressors and driven by circulating steroid hormones. A key issue has been how to identify and care for aggressively developing prostate tumours. Here we discuss how expression of the splicing regulators ESRP1 and ESRP2, and how their role as "masterminds" of epithelial splicing patterns, have been identified as markers of aggressively proliferating prostate primary tumours. We suggest that the origin of prostate cancer within epithelial cells, and the subsequent association of ESRP1 and ESRP2 expression with more aggressive disease progression, identify ESRP1 and ESRP2 as lineage survival oncogenes. To move this field on in the future it will be important to identify the gene expression targets controlled by ESRP1/2 that regulate prostate cancer proliferation. Potential future therapies could be designed to target ESRP1 and ESRP2 protein activity or their regulated splice isoforms in aggressive prostate tumours. Design of these therapies is potentially complicated by the risk of producing a more mesenchymal splicing environment that might promote tumour metastasis.

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“…In hormone-dependent cancers such as breast and prostate cancers, ESRP1 expression was shown to be associated with steroid hormone signaling. Public transcriptome and chromatin immunoprecipitation-sequencing data analyses revealed that ESRP1 expression correlates with ESR1 expression in breast cancer, and ERα binding sites are located within the ESRP1 promoter, suggesting that ESRP1 expression is regulated by ERα signaling in breast cancer [ 82 ]. Similarly, androgen levels were found to regulate ESRP1 expression.…”

Section: Esrp1 Regulation In Cancermentioning

confidence: 99%

Role of epithelial splicing regulatory protein 1 in cancer progression

Kwon

2023

Cancer Cell Int

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As aberrant alternative splicing by either dysregulation or mutations of splicing factors contributes to cancer initiation and progression, splicing factors are emerging as potential therapeutic targets for cancer therapy. Therefore, pharmacological modulators targeting splicing factors have been under development. Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific splicing factor, whose downregulation is associated with epithelial–mesenchymal transition (EMT) by regulating alternative splicing of multiple genes, such as CD44, CTNND1, ENAH, and FGFR2. Consistent with the downregulation of ESRP1 during EMT, it has been initially revealed that high ESRP1 expression is associated with favorable prognosis and ESRP1 plays a tumor-suppressive role in cancer progression. However, ESRP1 has been found to promote cancer progression in some cancers, such as breast and ovarian cancers, indicating that it plays a dual role in cancer progression depending on the type of cancer. Furthermore, recent studies have reported that ESRP1 affects tumor growth by regulating the metabolism of tumor cells or immune cell infiltration in the tumor microenvironment, suggesting the novel roles of ESRP1 in addition to EMT. ESRP1 expression was also associated with response to anticancer drugs. This review describes current understanding of the roles and mechanisms of ESRP1 in cancer progression, and further discusses the emerging novel roles of ESRP1 in cancer and recent attempts to target splicing factors for cancer therapy.

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A Regulatory Axis between Epithelial Splicing Regulatory Proteins and Estrogen Receptor α Modulates the Alternative Transcriptome of Luminal Breast Cancer

Cited by 6 publications

References 71 publications

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease

Proteomic analysis of pulmonary arteries and lung tissues from dogs affected with pulmonary hypertension secondary to degenerative mitral valve disease

Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer

Role of epithelial splicing regulatory protein 1 in cancer progression

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