Semaphorin 3C as a Therapeutic Target in Prostate and Other Cancers

Hui, Daniel; Tam, Kevin J.; Jiao, Ivy Z F; Ong, Christopher J.

doi:10.3390/ijms20030774

Cited by 21 publications

(15 citation statements)

References 138 publications

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“…When assessing the potential biological importance of the analyzed variants, SEMA3C stood out, jointly due to its large number of NCCMs and the existing literature suggesting that overexpression of SEMA3C is linked to poor prognosis in several cancer types including prostate cancer [55] and GBM [56]. In the topological associated domain (TAD; chr7:80.4-81.1 Mbp) that contains the SEMA3C gene, we found 14 NCCMs.…”

Section: Discussionmentioning

confidence: 91%

Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

et al. 2020

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Background: Glioblastoma (GBM) has one of the worst 5-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions. Results: We validate our GBM cohort, finding similar copy number aberrations and mutated genes based on coding mutations as previous studies. Performing analysis on non-coding constraint mutations and their position relative to nearby genes, we find a significant enrichment of non-coding constraint mutations in the neighborhood of 78 genes that have previously been implicated in GBM. Among them, SEMA3C and DYNC1I1 show the highest frequencies of alterations, with multiple mutations overlapping transcription factor binding sites. We find that a non-coding constraint mutation in the SEMA3C promoter reduces the DNA binding capacity of the region. We also identify 1776 other genes enriched for non-coding constraint mutations with likely regulatory potential, providing additional candidate GBM genes. The mutations in the top four genes, DLX5, DLX6, FOXA1, and ISL1, are distributed over promoters, UTRs, and multiple transcription factor binding sites. Conclusions: These results suggest that non-coding constraint mutations could play an essential role in GBM, underscoring the need to connect non-coding genomic variation to biological function and disease pathology.

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Section: Discussionmentioning

confidence: 91%

Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

et al. 2020

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“…Several semaphorin members have been reported to be upregulated in different advanced tumors and serve as potent tumor promoters, while others act as tumor suppressors (6, 19, 20). Among semaphorins, SEMA3C has been found to be associated with tumor progression and prognosis across multiple tumor types (6, 21, 22). It has been recently reported that SEMA3C drives the activation of multiple receptor tyrosine kinase pathways in prostate cancer cells, which is a key mechanism for mediating cancer growth, survival, and treatment resistance (10).…”

Section: Discussionmentioning

confidence: 99%

SEMA3C Promotes Cervical Cancer Growth and Is Associated With Poor Prognosis

et al. 2019

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Introduction: Aberrant activation of Semaphorin3C(SEMA3C) is widespread in human cancers. We aimed to analyze SEMA3C expression in cervical cancer and investigate the role of SEMA3C in cervical cancer and its underlying mechanism, which is important for exploring new therapeutic targets and prognostic factors.Materials and Methods: The expression of SEMA3C was examined in paraffin-embedded cervical cancer specimens. In vivo and in vitro assays were performed to validate the effect of SEMA3C on cervical cancer cell proliferation and p-ERK pathway activation. Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data set.Results: SEMA3C expression was associated with poor survival in both the TCGA cohort and our cohort. Silencing of SEMA3C suppressed cervical cancer cell proliferation, colony formation ability, and the activation of the p-ERK signaling pathway in vitro. SEMA3C depletion inhibited tumor growth in vitro. GSEA also showed that the epithelial mesenchymal transition (EMT), TGFβ signaling pathway, angiogenesis, and extracellular matrix (ECM) receptor interactions are associated with a high SEMA3C expression phenotype.Conclusion: SEMA3C is correlated with poor prognosis of cervical cancer patients and promotes tumor growth via the activation of the p-ERK pathway.

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“…Semaphorin-3C (SEMA3C) promotes prostate cancer growth by transactivating multiple receptor tyrosine kinases (RTK), including EGFR, via Plexin B1 receptor which has intrinsic GAP activity [ 57 ]. Furthermore, the overexpression of SEMA3C is associated with unfavorable outcomes in a wide spectrum of tumors, including glioma, breast, lung, liver, pancreatic, stomach and gynecological cancers [ 58 ]. STEAP4 encodes for a member of the six transmembrane epithelial antigen of prostate (STEAP) family, which functions as a metalloreductase and may promote prostate and colorectal cancer development [ 59 , 60 ].…”

Section: Novel Scc-associated Markersmentioning

confidence: 99%

Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment

Lazăr

Dinescu

Costache

2020

JCM

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Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients’ life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic cSCC displays considerable aggressiveness leading to the death of affected individuals. No consensus has been reached as to which features better characterize the aggressive behavior of cSCC, an achievement hindered by the high mutational burden caused by chronic ultraviolet light exposure. Even though some subtypes have been recognized as high risk variants, depending on certain tumor features, cSCC that are normally thought of as low risk could pose an increased danger to the patients. In light of this, specific genetic and epigenetic markers for cutaneous SCC, which could serve as reliable diagnostic markers and possible targets for novel treatment development, have been searched for. This review aims to give an overview of the mutational landscape of cSCC, pointing out established biomarkers, as well as novel candidates, and future possible molecular therapies for cSCC.

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Semaphorin 3C as a Therapeutic Target in Prostate and Other Cancers

Cited by 21 publications

References 138 publications

Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes

SEMA3C Promotes Cervical Cancer Growth and Is Associated With Poor Prognosis

Deciphering the Molecular Landscape of Cutaneous Squamous Cell Carcinoma for Better Diagnosis and Treatment

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