Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system

Huang, Yuping; Liao, Junguang; Vlashi, Rexhina; Chen, Guiqian

doi:10.1016/j.cellsig.2023.110852

Cited by 16 publications

(5 citation statements)

References 151 publications

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“…In contrast, gene sets on apoptosis and specific immune responses were negatively enriched (Figure 3B ). KEGG enrichment analysis of the DEGs highlighted pathways vital for OSA progression (Figure 3C ), including PI3K–Akt signalling, 45 cytokine–cytokine receptor interaction, 46 osteoclast differentiation, 47 focal adhesion 48 and extracellular matrix (ECM)‐receptor interaction. 49 An enrichment map highlighted a significant cluster incorporating the PI3K–Akt signalling pathway, focal adhesion and ECM‐receptor interaction (Figure 3D ).…”

Section: Resultsmentioning

confidence: 99%

Identifying squalene epoxidase as a metabolic vulnerability in high‐risk osteosarcoma using an artificial intelligence‐derived prognostic index

Wang,

Ma,

et al. 2024

Clinical & Translational Med

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BackgroundOsteosarcoma (OSA) presents a clinical challenge and has a low 5‐year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers to stratify high‐risk OSA patients and guide treatment.MethodsWe combined 10 machine‐learning algorithms into 101 combinations, from which the optimal model was established for predicting overall survival based on transcriptomic profiles for 254 samples. Alterations in transcriptomic, genomic and epigenomic landscapes were assessed to elucidate mechanisms driving poor prognosis. Single‐cell RNA sequencing (scRNA‐seq) unveiled genes overexpressed in OSA cells as potential therapeutic targets, one of which was validated via tissue staining, knockdown and pharmacological inhibition. We characterized changes in multiple phenotypes, including proliferation, colony formation, migration, invasion, apoptosis, chemosensitivity and in vivo tumourigenicity. RNA‐seq and Western blotting elucidated the impact of squalene epoxidase (SQLE) suppression on signalling pathways.ResultsThe artificial intelligence‐derived prognostic index (AIDPI), generated by our model, was an independent prognostic biomarker, outperforming clinicopathological factors and previously published signatures. Incorporating the AIDPI with clinical factors into a nomogram improved predictive accuracy. For user convenience, both the model and nomogram are accessible online. Patients in the high‐AIDPI group exhibited chemoresistance, coupled with overexpression of MYC and SQLE, increased mTORC1 signalling, disrupted PI3K–Akt signalling, and diminished immune infiltration. ScRNA‐seq revealed high expression of MYC and SQLE in OSA cells. Elevated SQLE expression correlated with chemoresistance and worse outcomes in OSA patients. Therapeutically, silencing SQLE suppressed OSA malignancy and enhanced chemosensitivity, mediated by cholesterol depletion and suppression of the FAK/PI3K/Akt/mTOR pathway. Furthermore, the SQLE‐specific inhibitor FR194738 demonstrated anti‐OSA effects in vivo and exhibited synergistic effects with chemotherapeutic agents.ConclusionsAIDPI is a robust biomarker for identifying the high‐risk subset of OSA patients. The SQLE protein emerges as a metabolic vulnerability in these patients, providing a target with translational potential.

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Section: Resultsmentioning

confidence: 99%

Identifying squalene epoxidase as a metabolic vulnerability in high‐risk osteosarcoma using an artificial intelligence‐derived prognostic index

Wang,

Ma,

et al. 2024

Clinical & Translational Med

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“…Integrins bind to ECM proteins such as laminin and fibronectin in the extracellular domain, whereas the intracellular domain binds various signaling factors and actinbinding proteins directly or indirectly [15][16][17]. Integrins themselves do not exert any kinase activity, but when cells bind extracellular matrix proteins via integrins, FAK, an intracellular domain-binding protein of integrins, is activated, leading to mitogen-(MAP) kinase activation, thereby regulating cell proliferation as well as PI3-Akt pathway and Rho family small G protein activation, which regulate cell survival and cell motility and intracellular skeletal reorganization, respectively [18][19][20][21][22]53]. We previously described that culturing integrin αV-overexpressing SCCKN cells transfected with the αV gene on type I collagen induced rapid FAK, MEK, and ERK1/ 2 phosphorylation compared to the control [36].…”

Section: Discussionmentioning

confidence: 99%

“…The extracellular integrin domain bind ECM proteins while the intracellular binds various cytoskeletal proteins (e.g., talin, α-actinin, and actin filaments) as ECM protein receptors [15][16][17]. Furthermore, integrins activate focal adhesion kinase (FAK) bound to their intracellular domain β-chain by binding extracellular substrate proteins, thereby transducing various signals [18][19][20][21][22]. Therefore, integrins are not only adhesion molecules between cellular and ECM proteins but also pivotal for organogenesis and tissue differentiation by regulating cell morphology, motility, proliferation, differentiation, and other signal transduction processes [23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study

Sakurai,

Ishida,

Shintani

et al. 2024

Pathol. Oncol. Res.

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Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and β-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive.Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, β1, β3, β5, β6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated.Results: We observed immunohistochemical integrin αV, β1, β6, β8, and FAK expressions in the cell membrane and cytoplasm but not integrin β3 and β5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin β8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed.Conclusion: Our results indicate that pFAK and integrin β8 are prognostic factors for OSCC. Therefore, pFAK- and integrin β8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.

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“…For instance, capsule polysaccharide synthetase Cap8J regulates capsule formation, and the flagellar synthesis regulator and CobQ/CobB/ MinD/ParA family play a pivotal role in polar flagella expression and virulence [ 29 – 31 ]. Studies have shown that a MinD mutant of Escherichia coli O157: H7 reduces its adhesion to human epithelial cells [ 32 – 35 ]. Li et al demonstrated that the minD mutation in Aeromonas hydrophila could lead to abnormal cell division and reduce the adhesion, biofilm formation, and bacterial motility [ 36 – 38 ].…”

Section: Discussionmentioning

confidence: 99%

Genome Sequencing Analysis of a Rare Case of Blood Infection Caused by Flavonifractor plautii

Chen,

Bi,

Ruan

et al. 2024

Am J Case Rep

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Objective:Rare disease Background:Flavonifractor plautii belongs to the clostridium family, which can lead to local infections as well as the bloodstream infections. Flavonifractor plautii caused infection is rarely few in the clinic. To understand better Flavonifractor plautii, we investigated the drug sensitivity and perform genome sequencing of Flavonifractor plautii isolated from blood samples in China and explored the drug resistance and pathogenic mechanism of the bacteria. Case report:The Epsilometer test method was used to detect the sensitivity of flavonoid bacteria to antimicrobial agents. PacBio sequencing technology was employed to sequence the whole genome of Flavonifractor plautii, and gene prediction and functional annotation were also analyzed. Flavonifractor plautii displayed sensitivity to most drugs but resistance to fluoroquinolones and tetracycline, potentially mediated by tet (W/N/W). The total genome size of Flavonifractor plautii was 4,573,303 bp, and the GC content was 59.78%. Genome prediction identified 4,506 open reading frames, including 9 ribosomal RNAs and 66 transfer RNAs. It was detected that the main virulence factor-coding genes of the bacteria were the capsule, polar flagella and FbpABC, which may be associated with bacterial movement, adhesion, and biofilm formation. Conclusions:The results of whole-genome sequencing could provide relevant information about the drug resistance mechanism and pathogenic mechanism of bacteria and offer a basis for clinical diagnosis and treatment.

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Focal adhesion kinase (FAK): its structure, characteristics, and signaling in skeletal system

Cited by 16 publications

References 151 publications

Identifying squalene epoxidase as a metabolic vulnerability in high‐risk osteosarcoma using an artificial intelligence‐derived prognostic index

Identifying squalene epoxidase as a metabolic vulnerability in high‐risk osteosarcoma using an artificial intelligence‐derived prognostic index

Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study

Genome Sequencing Analysis of a Rare Case of Blood Infection Caused by Flavonifractor plautii

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