Recurrent fusion transcripts in squamous cell carcinomas of the vulva

Brunetti, Marta; Agostini, Antonio; Davidson, Ben; Tropé, Claes G.; Heim, Sverre; Panagopoulos, Ioannis; Micci, Francesca

doi:10.18632/oncotarget.15167

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…Finally, GPR137B is to our knowledge unique in that its expression can increase both Rag and mTORC1 localization to lysosomes even in the absence of amino acids, and regulate a dynamic cycle of RagA activation and lysosome dissociation. Given the key roles of mTORC1 signaling in many cancers, it is interesting that a few reports, without providing molecular mechanisms, have suggested a link from GPR137 and GPR137B to different types of cancers 55–58 . Together with our mechanistic results on GPR137B’s role in Rag and mTORC1 regulation, this suggests that the three human GPCR-like GPR137 genes are potential therapeutic targets for cancers that depend on RagA and/or mTORC1 signaling for growth and survival.…”

Section: Discussionmentioning

confidence: 99%

The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity

et al. 2019

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Cell growth is controlled by a lysosomal signaling complex containing Rag small GTPases and mTORC1 kinase. Here we carried out a microscopy-based genome-wide human siRNA screen and discovered a lysosome-localized G-protein coupled receptor (GPCR)-like protein, GPR137B, that interacts with Rag GTPases, increases Rag localization and activity, and thereby regulates mTORC1 translocation and activity. High GPR137B expression can recruit and activate mTORC1 in the absence of amino acids. Furthermore, GPR137B also regulates the dissociation of activated Rag from lysosomes, suggesting that GPR137B controls a cycle of Rag activation and dissociation from lysosomes. GPR137B knockout cells exhibited defective autophagy and an expanded lysosome compartment, similar to Rag knockout cells. Like zebrafish RagA mutants, GPR137B mutant zebrafish had upregulated TFEB target gene expression and an expanded lysosome compartment in microglia. Thus, GPR137B is a GPCR-like lysosomal regulatory protein that controls dynamic Rag and mTORC1 localization and activity as well as lysosome morphology.

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Section: Discussionmentioning

confidence: 99%

The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity

et al. 2019

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“…This search for a novel therapy is confirmed by increasing numbers of studies. Brunetti et al (2017) [284] studied the juxtaposition of two different genes or gene parts due to chromosomal rearrangement, which is a well-known neoplasia-associated pathogenetic mechanism, and found two recurrent fusions with STIP1-CREB3L1 and ZDHHC5-GPR137 present in VSCC. The transcripts were detected only in the tumour samples, not in normal vulvar tissue from healthy controls.…”

Section: Advancements In Vc Therapy Based On Better Profiling and Novmentioning

confidence: 99%

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology

Žúbor

Wang

Líšková

et al. 2020

IJMS

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Vulvar cancer (VC) is a specific form of malignancy accounting for 5–6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as “plasma medicine” and “plasma oncology”. This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered.

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“…The neighboring genes of C1orf74 are TRAF3IP3 and IRF6 [28]. Fusion transcripts of C1orf74 and neighboring IRF6 have been reported previously in squamous cell carcinomas [29]. The C1orf74 protein is found in both cytoplasm as well as plasma membrane but its function in normal and cancer cells remains unknown [25].…”

Section: Introductionmentioning

confidence: 99%

Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer

Parida,

Lewis,

Sharan

et al. 2023

Cells

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C1orf74, also known as URCL4, has been reported to have higher expression and be associated with poor prognosis in lung adenocarcinoma patients, and its role in regulation of the EGFR/AKT/mTORC1 pathway has been recently elucidated. In the current study, we used publicly available data and experimental validation of C1orf74 gene expression and its association with prognosis in cervical cancer patients. qRT-PCR was performed using RNA from cervical cancer cell lines and twenty-five cervical cancer patients. Data from TNMplot revealed that mRNA expression of the C1orf74 gene in primary tumor tissues, as well as metastatic tissues from cervical cancer patients, was significantly higher compared to normal cervical tissues. HPV-positive tumors had higher expression of this gene compared to HPV-negative tumors. qPCR analysis also demonstrated higher expression of C1orf74 in HPV-positive cervical cancer cell lines and most cervical cancer patients. The promoter methylation levels of the C1orf74 gene in cervical cancer tissues were lower compared to normal cervical tissues (p < 0.05). Collectively, our study indicates that higher expression of the C1orf74 gene caused by hypomethylation of its promoter is associated with poor overall survival in cervical cancer patients. Thus, C1orf74 is a novel prognostic marker in cervical cancer.

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Recurrent fusion transcripts in squamous cell carcinomas of the vulva

Cited by 4 publications

References 22 publications

The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity

The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology

Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer

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