ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway

Yuan, Hongyu; Zhou, Wei; Yang, Yang; Xue, Liyan; Liu, Linxiu; Song, Yongmei

doi:10.1016/j.yexcr.2018.03.017

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…ISG15 plays an apparently contradictory role in cancers. On one side, ISG15 is highly expressed and functions as a tumour-promoting molecule in some cancers, 7,10,36,37 and its high expression contributes to cancer progression, including oesophageal, 38 oral, 39 nasopharyngeal 11 and pancreatic cancer. 7 It has been reported that free ISG15 promotes cancer stem cell-like phenotypes of PDAC via autocrine 40 and paracrine-mediated pattern.…”

Section: Discussionmentioning

confidence: 99%

ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer

Zhang

Wang

Qiao

et al. 2021

J Cellular Molecular Medi

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High morbidity and mortality make ovarian cancer the most deadly gynaecologic cancer. 1 Platinum-based chemotherapy following optimal surgical excision of the tumour is currently considered as the standard therapy for ovarian cancer. Even though most ovarian cancers initially respond to chemotherapy with relative sensitivity, drug resistance is often developed during clinical chemotherapy, thereby leading to shorter overall survival and worse prognosis. 2 Consequently, it is critical to develop effective strategies to improve cancer treatment outcomes.Interferon-stimulated Gene 15 (ISG15) is a type I interferoninducible gene and implicated in interferon-induced immune responses. 3 ISG15 is also known as ubiquitin cross-reactive protein (UCRP), and its structure is very similar to ubiquitin. 4,5 Much like ubiquitination, a process called ISGylation can be undertaken by conjugation of ISG15 to a lysine residue in the target proteins by enzyme cascade reaction. 6 Recently, it has been reported that ISG15 plays a strikingly ambiguous role in cancers. Free ISG15 and conjugated ones are increased and acted as important oncoproteins. [7][8][9][10][11][12] On the other hand, ISG15 suppresses tumour progression by regulating the production of IFNγ and the functions of natural killer cells, enhancing E3 ubiquitin ligase activity of the carboxyl terminus

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Section: Discussionmentioning

confidence: 99%

ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer

Zhang

Wang

Qiao

et al. 2021

J Cellular Molecular Medi

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“…50 showed already in 1996 that administration of IFNβ to healthy individuals increased serum ISG15 levels significantly, and suggested that free ISG15 may represent an important mediator of the host response to IFN α/β by amplifying the immunomodulatory effects of IFNs. ISG15 has later been suggested as biomarker and/or target for treatment in human diseases such as systemic lupus erythematosus, 51 active tuberculosis, 20 oesophageal squamous cell carcinoma, 52 and pancreatic cancer. 53 Treatment with IFNβ in IBD has shown contradictory results, 7 but inhibition of the JAK-STAT pathway represents a promising therapeutic target for moderate to severe UC.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Epithelial Cells Express Immunomodulatory ISG15 During Active Ulcerative Colitis and Crohn’s Disease

Østvik

Svendsen

Granlund

et al. 2020

Journal of Crohn's and Colitis

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Background and Aims Intestinal epithelial cells [IECs] secrete cytokines that recruit immune cells to the mucosa and regulate immune responses that drive inflammation in inflammatory bowel disease [IBD]. However, experiments in patient-derived IEC models are still scarce. Here, we aimed to investigate how innate immunity and IEC-specific pattern recognition receptor [PRR] signalling can be involved in an enhanced type I interferon [IFN] gene signature observed in colon epithelium of patients with active IBD, with a special focus on secreted ubiquitin-like protein ISG15. Methods Gene and protein expression in whole mucosa biopsies and in microdissected human colonic epithelial lining, in HT29 human intestinal epithelial cells and primary 3D colonoids treated with PRR-ligands and cytokines, were detected by transcriptomics, in situ hybridisation, immunohistochemistry, western blots, and enzyme-linked immunosorbent assay [ELISA]. Effects of IEC-secreted cytokines were examined in human peripheral blood mononuclear cells [PBMCs] by multiplex chemokine profiling and ELISA. Results The type I IFN gene signature in human mucosal biopsies was mimicked in Toll-like receptor TLR3 and to some extent tumour necrosis factor [TNF]-treated human IECs. In intestinal biopsies, ISG15 expression correlated with expression of the newly identified receptor for extracellular ISG15, LFA-1 integrin. ISG15 was expressed and secreted from HT29 cells and primary 3D colonoids through both JAK1-pSTAT-IRF9-dependent and independent pathways. In experiments using PBMCs, we show that ISG15 releases IBD-relevant proinflammatory cytokines such as CXCL1, CXCL5, CXCL8, CCL20, IL1, IL6, TNF, and IFNγ. Conclusions ISG15 is secreted from primary IECs upon extracellular stimulation, and mucosal ISG15 emerges as an intriguing candidate for immunotherapy in IBD.

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“…proposed that ISG15 can promote the proliferation, invasion and migration of esophageal squamous cell carcinoma via c-MET/Fyn/β-catenin pathway [35]. Li XX et al reported that TROP2 may promote the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT [36].…”

Section: Discussionmentioning

confidence: 99%

TROP2 modulates the progression in papillary thyroid carcinoma

et al. 2021

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Background: Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear. Methods: The expressions of TROP2 in PTC and control tissue were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The proliferation and invasion of PTC cell lines were examined by cell cloning and transwell assays. RNA sequencing analysis and public data analysis were assessed to investigate the potential mechanisms of TROP2 in PTC. Gene correlation analysis was conducted to explore the association between TROP2 and the related gene ISG15 in patients with PTC. Results: The expression of TROP2 was significantly higher in PTC than control. The high expression of TROP2 protein was associated with lymph node metastasis, tumor size and capsular infiltration (P<0.05). SiRNA-mediated TROP2 gene expression silencing can significantly inhibit proliferation and migration of PTC cells. ISG15 decreased in TROP2 siRNA PTC cells and increased in PTC patients significantly. There was a significant correlation between the expression of TROP2 and ISG15 in PTC patients. TROP2 interacted directly with ATP6V1A, CEBPA and SOX5 and then further interacted with the immune genes. TROP2 expression and tumor-infiltrating immune cells were also correlated in thyroid cancer microenvironment. Conclusions: TROP2 promotes the development of PTC. TROP2 expression was correlated with ISG15 and tumor-infiltrating immune cells in thyroid cancer.

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ISG15 promotes esophageal squamous cell carcinoma tumorigenesis via c-MET/Fyn/β-catenin signaling pathway

Cited by 22 publications

References 32 publications

ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer

ISG15 is downregulated by KLF12 and implicated in maintenance of cancer stem cell‐like features in cisplatin‐resistant ovarian cancer

Intestinal Epithelial Cells Express Immunomodulatory ISG15 During Active Ulcerative Colitis and Crohn’s Disease

TROP2 modulates the progression in papillary thyroid carcinoma

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