Redefining PTB domain into independently functional dual cores

Zhang, Jun; Padarti, Akhil; Jiang, Xiaoting; Abou‐Fadel, Johnathan

doi:10.1016/j.bbrc.2020.01.114

Cited by 6 publications

(4 citation statements)

References 16 publications

(39 reference statements)

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“…These studies support the hypothesis that KRIT1 could regulate leukocyte adhesion in general, yet a more recent study reported that CCM3 regulates the release of the 'reserved' pool of granules from neutrophils due to its interaction with the serine/threonine kinase-24 (STK24) [38]. Though the impact of the interaction of CCM3 with STK24 vs. with KRIT1/CCM2 is still in debate [39][40][41], these findings demonstrate that CCM proteins can regulate neutrophil-specific functions. Together, the role of KRIT1 in limiting the response to inflammatory stimuli [25] and the high expression of KRIT1 in neutrophils and other myeloid cells (data not shown), combined with the potential for KRIT1 to regulate neutrophil adhesion via binding to Rap1 [31] or ICAP1a [32][33][34][35][36][37], led us to explore a potential role for KRIT1 in regulating neutrophil function.…”

Section: Introductionsupporting

confidence: 70%

KRIT1‐mediated regulation of neutrophil adhesion and motility

2022

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Loss of Krev interaction‐trapped‐1 (KRIT1) expression leads to the development of cerebral cavernous malformations (CCM), a disease in which abnormal blood vessel formation compromises the structure and function of the blood–brain barrier. The role of KRIT1 in regulating endothelial function is well‐established. However, several studies have suggested that KRIT1 could also play a role in regulating nonendothelial cell types and, in particular, immune cells. In this study, we generated a mouse model with neutrophil‐specific deletion of KRIT1 in order to investigate the effect of KRIT1 deficiency on neutrophil function. Neutrophils isolated from adult Ly6Gtm2621(cre)Arte Krit1flox/flox mice had a reduced ability to attach and spread on the extracellular matrix protein fibronectin and exhibited a subsequent increase in migration. However, adhesion to and migration on ICAM‐1 was unchanged. In addition, we used a monomeric, fluorescently‐labelled fragment of fibronectin to show that integrin activation is reduced in the absence of KRIT1 expression, though β1 integrin expression appears unchanged. Finally, neutrophil migration in response to lipopolysaccharide‐induced inflammation in the lung was decreased, as shown by reduced cell number and myeloperoxidase activity in lavage samples from Krit1PMNKO mice. Altogether, we show that KRIT1 regulates neutrophil adhesion and migration, likely through regulation of integrin activation, which can lead to altered inflammatory responses in vivo.

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Section: Introductionsupporting

confidence: 70%

KRIT1‐mediated regulation of neutrophil adhesion and motility

2022

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“…It is made biomarkers, providing insights into the progression of the disease. Finally, elevated CCM protein levels in tumors night suggest their viability as biomarkers across multiple cancers [49][50][51][52][53][54][55][56][57][58][59]. Both main types of progesterone receptors (nPRs and mPRs) might serve as potential biomarkers for genetically influenced diverse cancer subtypes [60][61][62][63][64][65][66][67][68].…”

Section: Introductionmentioning

confidence: 99%

Identification of Cholangiocarcinoma (CCA) Subtype-Specific Biomarkers

Croft,

Gao,

Quintanar

et al. 2023

Preprint

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Liver cancer ranks sixth globally in diagnoses and second in cancer-related deaths. Cholangiocarcinoma (CCA), a relatively rare cancer originating from bile duct epithelium, constitutes 2% of all cancers, with increasing occurrences in Westerns. Incidence is influenced by inflammation, genetics, risk factors, and regional disparities, with higher rates in the Eastern hemisphere. Diagnostic and prognostic biomarkers are pivotal for effective cancer prevention and management. Recent research explores serum proteins for non-invasive CCA diagnosis and proposes targeted receptor approaches for therapeutics.This study aims to identify these biomarkers via bioinformatics analysis of public datasets, focusing on CCA patient transcriptomes to uncover gene biomarkers linked to age and survival. Pathway analysis reveals functions and pathways associated with these biomarkers. Additionally, the study employs the ESM-TFpredict machine learning model to predict transcription factors (TFs) using protein sequence data.Leveraging publicly available data enhances our understanding of liver cancer’s molecular profiles and clinical relevance, particularly concerning CCA, This study integrates bioinformatics analysis, transcriptomic exploration, and machine learning to unveil a novel set of potential diagnostic and prognostic biomarkers for CCA.

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“…Pathway analysis illuminated functions and disrupted pathways related to these biomarkers, providing insights into disease progression. Additionally, altered CCM protein levels in tumors propose their potential as biomarkers spanning multiple cancers [20,[53][54][55][56][57][58][59][60][61][62][63]. Both progesterone receptor types (nPRs and mPRs) could potentially serve as biomarkers for genetically influenced cancer subtypes [20,[61][62][63][64][65].…”

Section: Introductionmentioning

confidence: 99%

Novel hepatocellular carcinomas (HCC) Subtype-Specific Biomarkers

Croft,

Quintanar,

Gao

et al. 2023

Preprint

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IntroductionHepatocellular carcinoma (HCC), the most common form of liver cancer, is a global health concern and a leading cause of cancer-related deaths. HCC accounts for a significant portion of liver cancers and has low survival rates of 5% to 30%, especially for HCC patients with a survival rate of 15%. Early detection is challenging due to the absence of symptoms in the early stages. The complexity and molecular diversity of HCC contribute to its poor prognosis. Understanding its molecular subtypes and mechanisms is crucial for improved management.MethodsThe study utilized publicly available data to investigate the potential diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) based on their transcript per million (TPM) expression levels. A dataset of 407 HCC patient profiles was analyzed for survival trends and gene expression patterns.ResultsThrough a comprehensive approach, over 900 potential prognostic candidates were identified. Further analysis narrowed down 647 prognostic and diagnostic candidate biomarkers. The study also explored the role of the CmPn signaling network in HCC, reaffirming that its components could act as prognostic markers. Additionally, the study-utilized machine learning to discover 102 transcription factors (TFs) associated with HCC, from candidate biomarkers.ConclusionsThe findings provide insights into the molecular basis of HCC and offer potential avenues for improved diagnosis, treatment, and patient outcomes. The expanded prognostic biomarker pool aids in pinpointing HCC-specific grading and staging biomarkers, facilitating targeted therapies for improved patient outcomes and survival rates

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Redefining PTB domain into independently functional dual cores

Cited by 6 publications

References 16 publications

KRIT1‐mediated regulation of neutrophil adhesion and motility

KRIT1‐mediated regulation of neutrophil adhesion and motility

Identification of Cholangiocarcinoma (CCA) Subtype-Specific Biomarkers

Novel hepatocellular carcinomas (HCC) Subtype-Specific Biomarkers

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