Ubiquitin-Specific Peptidase 18: A Multifaceted Protein Participating in Breast Cancer

Tecalco-Cruz, Ángeles C.; Ramírez-Jarquín, Josué O.; Zepeda–Cervantes, Jesús; Solleiro-Villavicencio, Helena; Abraham-Juárez, María Jazmín

doi:10.36255/exon-publications-breast-cancer-usp18

Cited by 1 publication

(1 citation statement)

References 82 publications

(116 reference statements)

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“…Specifically in tumorigenesis, the roles of free ISG15 and ISGylation are not well‐defined, despite many studies. Some studies suggest that protein ISGylation is an antagonistic system to the ubiquitination system in order to provide stability to proteins in breast cancer cells (Pinto‐Fernandez et al., 2021 ; Tecalco‐Cruz et al., 2022 ). Concurrent to the above findings, we have shown that ISGylation of STAT3 in ascites cells may be contributing to its stability and increasing the sEV release.…”

Section: Discussionmentioning

confidence: 99%

ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis

Dorayappan,

Wagner,

Park

et al. 2024

J of Extracellular Bio

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The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian cancer progression and metastasis is largely unknown. In high grade serous ovarian cancer (HGSOC), ascites is the major contributor to peritoneal metastasis. In this study, we identified significantly elevated ISG15 protein expression in HGSOC patient ascites, ascites derived primary ovarian cancer cells (POCCs), POCC small extracellular vesicles (sEVs) as well as metastatic tissue. Our results demonstrates that ISG15 increases exocytosis in ascites‐derived POCCs by decreasing the endosome‐lysosomal fusion, indicating a key role in sEV secretion. Further, knockdown (KD) of ISG15 resulted in a significant decrease in vesicles secretion from HGSOC cells and in vivo mouse models, leading to reduced HGSOC cell migration and invasion. Furthermore, our pre‐clinical mouse model studies revealed the influence of vesicular ISG15 on disease progression and metastasis. In addition, knockdown of ISG15 or using the ISG15 inhibitor, DAP5, in combination therapy with carboplatin showed to improve the platinum sensitivity in‐vitro and reduce tumour burden in‐vivo. We also found that ISG15 expression within sEV represents a promising prognostic marker for HGSOC patients. Our findings suggest that ISG15 is a potential therapeutic target for inhibiting progression and metastasis in HGSOC and that vesicular ISG15 expression could be a promising biomarker in the clinical management of ovarian cancer.Significance: High‐grade serous ovarian cancer (HGSOC) has high morbidity and mortality rates, but its progression and metastasis are still poorly understood, and there is an urgent need for early detection and targeted therapies. Our study presents novel findings that implicate ISG15‐mediated vesicular proteins in the advancement and spread of HGSOC. These results offer pre‐clinical evidence of potential new molecular targets, prognostic markers and therapeutic strategies for HGSOC that could ultimately enhance patient survival.

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Section: Discussionmentioning

confidence: 99%

ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis

Dorayappan,

Wagner,

Park

et al. 2024

J of Extracellular Bio

View full text Add to dashboard Cite

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Ubiquitin-Specific Peptidase 18: A Multifaceted Protein Participating in Breast Cancer

Abstract: published in pdf, html, and xml formats as shown under Catalogue upon editorial acceptance of all chapters. The citation details will not change even after the publication of the book in its final format.

Cited by 1 publication

References 82 publications

ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis

ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis

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