Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer

Roseweir, Antonia K.; Powell, Arfon; Horstman, Sheryl L.; Inthagard, Jitwadee; Park, James H.; Horgan, Paul G.; Edwards, Joanne

doi:10.1016/j.cellsig.2019.01.007

Cited by 49 publications

(48 citation statements)

References 36 publications

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“…HCK gene encodes the hematopoietic cell kinase protein, which is a member of the SRC family of cytoplasmic tyrosine kinases (SFK). SFKs have a similar protein domain organization, consisting of a unique domain at the N-terminal end, the Src homology 3 and 2 domains (SH3 and SH2), a domain with kinase activity and a C-terminal tail including a phosphorylation site for the cytoplasmic tyrosine kinase (CSK) [7][8][9].…”

Section: Resultsmentioning

confidence: 99%

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Whole Exome Sequencing Revealed a Candidate Gene for Finkelstein-Seidlmayer Disease

Bronz¹,

Gabriel²,

Lava³

et al. 2019

AJP

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Background: Finkelstein-Seidlmayer disease (FSD) is a benign cutaneous small-vessel leukocytoclastic vasculitis syndrome, which normally affects children between 2-60 months in a male-to-female ratio of 2:1. Skin lesions may appear as papules, erythematous macules, or urticaria. They are symmetric, sharp-edged and favouring the face, ears and extremities. Frequently they are targetoid, annular, medallion-like, or cockade. Fever and extracutaneous involvement are rare and spontaneous resolution occurs in 1-3 weeks. Case Information: In 2015, we reported a familial occurrence of FSD. Patients described in that article were the mother and all her three sons. All of them had a history of recurrent and relapsing nonthrombocytopenic, red-to-purpuric skin lesions, with a neonatal-onset. There was no systemic involvement. Anamnestic data revealed that maternal aunt, cousin and grandmother had also a positive history of neonatal onset of an acute cockade purpura and oedema. At that time, we suspected a genetic form of FSD with an autosomal dominant transmission or X-linked inheritance and incomplete penetrance. Method and Results: Blood samples were obtained from all available family members and a whole exome sequencing (WES) was performed on various affected and non-affected members of this family. The genetic analysis identified a common new mutation in the HCK gene. Conclusion: Up now, FSD is considered a sporadic disease and no genetic researches have been published on affected patients. We performed WES on a previously reported familiar case of FSD and the result was a common mutation in HCK gene. We found out the mutation on all the analysed affected and obligate-carrier members of the family. HCK gene encodes for a hematopoietic cell kinase protein, which is a member of the SRC family of cytoplasmic tyrosine kinases (SFK). We propose that HCK gene could be a candidate gene in the pathophysiology of some types of FSD. We also discuss the autosomal dominant transmission and incomplete penetrance of these specific types of disease.

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Section: Resultsmentioning

confidence: 99%

“…It may play a role in the degranulation of neutrophils. Aberrant activity has been reported in inflammation and cancer [9].…”

Section: Resultsmentioning

confidence: 99%

Whole Exome Sequencing Revealed a Candidate Gene for Finkelstein-Seidlmayer Disease

Bronz¹,

Gabriel²,

Lava³

et al. 2019

AJP

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“…SRC [V-Src Avian Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog] encodes the non-receptor protein tyrosine kinase, which plays a role in the regulation of cell proliferation, migration, and survival [28]. The SRC mutation is known to be involved in malignant progression [29,30]. Increased SRC activation is correlated with trastuzumab resistance and interacts with estrogen receptors.…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality using 32 Genes Commonly Involved in Breast Cancer: A Retrospective Study

Hung

Huang

Moi

2020

Preprint

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Background: Invasive ductal carcinoma (IDC) breast cancer is a heterogeneous disease characterized by multiple subtypes. Breast cancer survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on breast cancer prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC breast cancer to provide further understanding of the genetic characteristics associated with poor survival. Methods: The gene mutation profiles, baseline demographics, clinicopathological variables, and treatment characteristics of the early-stage breast cancer subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 32 genes commonly involved in breast cancer were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. Results: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates were 97.6%, 96.0%, and 68.2%, respectively. The high-risk group had a significantly higher risk of poor overall survival (adjusted hazard ratio = 9.94, 95% confidence interval = 2.24–44.20, P = 0.003) than the other groups and the low-risk group did not have a significantly higher risk of poor overall survival compared with controls. Conclusions: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 10 candidate genes selected are particularly involved in cell-cycle processes, DNA repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor survival outcomes.

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“…Hematopoietic cell kinase (HCK) is a member of the Src family of protein kinases, and is involved in various signal transduction pathways that regulate cell growth, proliferation, differentiation, migration, apoptosis [24]. In colorectal tumors, HCK is associated with prognosis and immune cell responses during local in ammation [25]. However, these genes are related to in ammatory response, immune response, cell migration and invasion, but none have been reported in preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Using Weighted Gene Co-Expression Network Analysis to Identify Key Genes Related to the Onset of Preeclampsia

Shen¹,

Wang²,

Zeng³

et al. 2020

Preprint

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Background: Preeclampsia is a form of hypertension in pregnancy, which induced by complicated factors. However, the pathogenesis of the disease is unclear. The present study was aimed to discover the critical biomarkers associated with the occurrence and development of preeclampsia. Methods：Gene data profile GSE75010 was downloaded from the Gene Expression Omnibus (GEO) database and used as discovery cohort to establish a WGCNA network determining significant modules which associated with clinical traits. Subsequently, functional enrichment analysis, pathway analysis and protein-protein interaction (PPI) network construction were performed on the core genes in significant modules to identify hub genes. Then, gene data profile GSE25906 was used as verified cohort to determine their diagnostic value of hub genes. The protein expression levels of these hub genes in preeclampsia and control placental tissues were verified using immunohistochemistry method. Finally, GSEA was performed to analyze their enrichment pathways. Results: Total 33 co-expression modules were identified after the establishment of WGCNA, of which 4 gene modules were identified as significant modules because they were related to multiple (>3) clinical traits. Total 75 core genes in significant modules were analyzed, and results showed that they were mainly enriched in adaptive immune response (Gene Ontology term) and platelet activation (Kyoto Encyclopedia of Genes and Genomes term). Finally, a total of 5 genes including TYROBP, PLEK, LCP2, HCK, ITGAM were identified as hub genes which scored high in PPI network and had high diagnostic value. Furthermore, the protein level of these 5 genes in placental tissues of preeclampsia was lower than that of the control group. Moreover, these 5 genes were all enriched in 17 pathways, including autoimmunity pathway. Conclusions：These 5 genes (TYROBP, PLEK, LCP2, HCK, ITGAM) may be closely related to the pathogenesis of preeclampsia, which may also help the diagnosis and therapy of preeclampsia.

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Src family kinases, HCK and FGR, associate with local inflammation and tumour progression in colorectal cancer

Cited by 49 publications

References 36 publications

Whole Exome Sequencing Revealed a Candidate Gene for Finkelstein-Seidlmayer Disease

Whole Exome Sequencing Revealed a Candidate Gene for Finkelstein-Seidlmayer Disease

Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality using 32 Genes Commonly Involved in Breast Cancer: A Retrospective Study

Using Weighted Gene Co-Expression Network Analysis to Identify Key Genes Related to the Onset of Preeclampsia

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