Association of the upregulated expression of focal adhesion kinase with poor prognosis and tumor dissemination in hypopharyngeal cancer

Omura, Go; Ando, Mizuo; Saito, Yuki; Kobayashi, Kenya; Yoshida, Masafumi; Ebihara, Yasuhiro; Kanaya, Kaori; Fujimoto, Chisato; Sakamoto, Takashi; Kondo, Kenji; Asakage, Takahiro; Yamasoba, Tatsuya

doi:10.1002/hed.24176

Cited by 10 publications

(7 citation statements)

References 33 publications

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“…As in our study, FAK overexpression has previously been reported in many cancers [42], including NSCLC and SCLC [19,33,34,43,44,45,46]. Moreover, FAK overexpression has been associated with poor survival in various cancers [12,14,20,22,47,48]. In NSCLC, however, discordant results have been reported.…”

Section: Discussionsupporting

confidence: 78%

“…Once activated by integrins, G protein-coupled receptor ligands, or growth factors and neuromediators, FAK is autophosphorylated at tyrosine 397 (Y397), then binds and activates downstream proteins such as Src, p130CAS, paxillin, and PI3KR2 [7,8,9], finally leading to cell adhesion, migration, invasion, survival, proliferation, angiogenesis, immune suppression, and regulation of DNA damage repair [8,9,10,11]. Because of these roles and its overexpression in many cancers, with the correlation to poor prognosis in some of them [12,13,14,15,16,17,18,19,20,21,22,23], FAK is believed to play a role in cancer development and progression. Small-molecule inhibitors targeting the FAK kinase domain (e.g., PF-573,228) have, therefore, been developed as potential anti-cancer targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

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Increased Expression and Activation of FAK in Small-Cell Lung Cancer Compared to Non-Small-Cell Lung Cancer

Nana

Hoton

Ambroise³

et al. 2019

Cancers

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Introduction: Focal adhesion kinase (FAK) plays a crucial role in cancer development and progression. FAK is overexpressed and/or activated and associated with poor prognosis in various malignancies. However, in lung cancer, activated FAK expression and its prognostic value are unknown. Methods: FAK and activated FAK (phospho-FAK Y397) expressions were analyzed by multiplex immunofluorescence staining in formalin-fixed paraffin-embedded tissues from 95 non-small-cell lung cancer (NSCLC) and 105 small-cell lung cancer (SCLC) patients, and 37 healthy donors. The FAK staining score was defined as the percentage (%) of FAK-stained tumor area multiplied by (×) FAK mean intensity and phospho-FAK staining score as the (% of phospho-FAK-stained area of low intensity × 1) + (% of phospho-FAK-stained area of medium intensity × 2) + (% of the phospho-FAK-stained area of high intensity × 3). FAK and phospho-FAK staining scores were compared between normal, NSCLC, and SCLC tissues. They were also tested for correlations with patient characteristics and clinical outcomes. Results: The median follow-up time after the first treatment was 42.5 months and 6.4 months for NSCLC and SCLC patients, respectively. FAK and phospho-FAK staining scores were significantly higher in lung cancer than in normal lung and significantly higher in SCLC compared to NSCLC tissues (p < 0.01). Moreover, the ratio between phospho-FAK and FAK staining scores was significantly higher in SCLC than in NSCLC tissues (p < 0.01). However, FAK and activated FAK expression in lung cancer did not correlate with recurrence-free and overall survival in NSCLC and SCLC patients. Conclusions: Total FAK and activated FAK expressions are significantly higher in lung cancer than in normal lung, and significantly higher in SCLC compared to NSCLC, but are not prognostic biomarkers in this study.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Increased Expression and Activation of FAK in Small-Cell Lung Cancer Compared to Non-Small-Cell Lung Cancer

Nana

Hoton

Ambroise³

et al. 2019

Cancers

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“…The full text of the remaining 42 citations was then carefully read, and twelve articles were subsequently excluded. Of the excluded articles, five employed an alternative survival endpoint instead of OS [ 23 – 27 ], five had no data available[ 8 , 13 – 14 , 28 – 30 ], one divided the FAK level into three or more groups [ 30 ], and one article treated FAK scores as a continuous variable[ 31 ]. A total of 30 studies were thus ultimately included in our meta-analysis ( Fig 1 ) [ 10 , 15 , 16 , 32 – 58 ].…”

Section: Resultsmentioning

confidence: 99%

Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis

Zeng

et al. 2016

PLoS ONE

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BackgroundRecently, the number of reports on focal adhesion kinase (FAK) as a vital therapeutic target in solid carcinomas has increased; however, the prognostic role of FAK status remains poorly understood. This study aims to evaluate the prognostic effect of FAK by means of a meta-analysis.MethodsWe performed a systematic literature search in order to examine the correlation between expression of FAK and overall survival(OS). The hazard ratio (HR) of OS was used to measure survival. A random-effects model was used to pool study statistics. Sensitivity and publication bias analyses were also conducted.ResultsThirty eligible studies involving 4702 patients were included. The median expression rate of FAK was 54%. Meta-analysis of the HRs demonstrated that high FAK expression was associated with worse OS (average HR = 2.073, 95%confidence interval[CI]:1.712–2.510, p = 0.000). Regarding cancer type, FAK was associated with worse OS in gastric cancer (HR = 2.646,95% CI:1.743–4.017, p = 0.000), hepatocellular carcinoma (HR = 1.788,95% CI:1.228–2.602, p = 0.002), ovarian cancer (HR = 1.815, 95% CI: 1.193–2.762, p = 0.005), endometrial cancer (HR = 4.149, 95% CI:2.832–6.079, p = 0.000), gliomas (HR = 2.650, 95% CI: 1.205–5.829, p = 0.015), and squamous cell carcinoma (HR = 1,696, 95% CI: 1.030–2.793, p = 0.038). No association was found between HR and disease staging according to our meta-regression analysis.ConclusionsOur study shows that high expression of FAK is associated with a worse OS in patients with carcinomas, but the association between FAK and prognosis varies according to cancer type. The value of FAK status in clinical prognosis in cancer needs further research.

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“…For example, upregulated FAK expression was correlated with poor prognosis and tumor dissemination in hypopharyngeal cancer patients [20]. Similarly, high FAK expression in triple-negative breast cancer was associated with lymphovascular invasion and shorter overall and progression free survival [21].…”

Section: Discussionmentioning

confidence: 99%

Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

Hou

Zhou

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Leupaxin (LPXN) is a member of the paxillin protein family. Several studies have reported that LPXN regulates cancer development; however, the role of LPXN in bladder cancer remains unknown. Methods: The expression of LPXN in bladder cancer cells and tissues was determined by real-time PCR, western blotting, and immunohistochemistry, respectively. The biological role of LPXN in bladder cancer cell proliferation, invasion, and angiogenesis was explored both in vitro and in vivo. Results: LPXN expression was elevated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. High LPXN expression was correlated with large tumor size, advanced tumor stage, and poor survival in bladder cancer patients. Overexpression of LPXN significantly promoted the proliferation, invasion, and angiogenesis of bladder cancer cells, while suppressing LPXN had the opposite effects. The impact on tumor progression was abolished by inhibiting PI3K/ AKT signaling pathway. We further demonstrated that LPXN probably up-regulated S100P via the PI3K/AKT pathway. Conclusions: LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer.

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Association of the upregulated expression of focal adhesion kinase with poor prognosis and tumor dissemination in hypopharyngeal cancer

Abstract: The current study demonstrated that upregulated FAK expression correlates with poor prognosis and tumor dissemination in surgically treated patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38:1164-1169, 2016.

Cited by 10 publications

References 33 publications

Increased Expression and Activation of FAK in Small-Cell Lung Cancer Compared to Non-Small-Cell Lung Cancer

Increased Expression and Activation of FAK in Small-Cell Lung Cancer Compared to Non-Small-Cell Lung Cancer

Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis

Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

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