Loss of the putative tumor suppressor protein spinophilin is associated with poor prognosis in head and neck cancer

Aigelsreiter, A.; Aigelsreiter, Ariane; Wehrschuetz, M.; Ress, Anna Lena; Koller, Karin; Salzwimmer, Michaela; Gerger, Armin; Schauer, Silvia; Bauernhofer, Thomas; Pichler, Martin

doi:10.1016/j.humpath.2013.11.014

Cited by 10 publications

(13 citation statements)

References 14 publications

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“…Despite recent advances in cancer therapy only 3% of cases are long‐term survivors . This can be explained by two facts: first, the majority of cases are diagnosed in an advanced disease stage with loco‐regional progression, and secondly, therapeutic options are still limited, with a high medical need for new therapeutic options and a deeper understanding of HNSCC biology …”

Section: Introductionmentioning

confidence: 99%

“…3 This can be explained by two facts: first, the majority of cases are diagnosed in an advanced disease stage with loco-regional progression, and secondly, therapeutic options are still limited, with a high medical need for new therapeutic options and a deeper understanding of HNSCC biology. [4][5][6] The Hedgehog Pathway (HhP) is a signal transduction pathway which is mainly known for its role in embryogenesis and wound healing. 7 However, in addition to its role in normal human development, it also plays an important role in cancer, including basal cell carcinoma (BCC), where selective inhibitors (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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AimsBecause the hedgehog signalling pathway plays a major role in many types of cancer and can nowadays be targeted by specific compounds, we aimed to investigate the role of this pathway in squamous cell carcinoma of the head and neck.Methods and resultsNinety‐eight treatment‐naive head and neck cancer specimens were immunohistologically stained for SMO, GLI‐1, p53 and p16 expression and correlated with clinicopathological factors. Immunoreactivity for SMO and GLI‐1 was found in 20 (20.4%) and 52 (53.1%) cases of tumours, respectively. SMO expression correlated with GLI‐1 expression (ρ = 0.258, P = 0.010) in univariate and multivariate analysis (P = 0.007, t = 2.81). In univariate analysis, high SMO expression was associated with shorter overall survival (HR = 0.56; 95% CI = 0.32–0.98; P = 0.044) and disease‐free survival (HR = 0.53; 95% CI = 0.30–0.95; P = 0.034). In multivariate cox regression analysis SMO expression showed a trend towards an independent predictor for shorter overall survival (HR = 0.57; 95% CI = 0.30–1.05; P = 0.072) and disease‐free survival (HR = 0.53; 95% CI = 0.28–1.02; P = 0.056). In head and neck cancer patients with low tumour p16 expression, SMO expression was an independent factor for overall survival (HR = 0.49; 95% CI = 0.24–0.98; P = 0.043) and disease‐free survival (HR = 0.45; 95% CI = 0.22‐0.96; P = 0.037).ConclusionAlthough it needs to be confirmed in larger cohorts, our results suggest that targeting SMO might be a potentially therapeutic option in patients with head and neck cancer. In line, molecular pathological analyses including mutation analysis in the hedgehog pathway might point to additional therapeutic leads.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

et al. 2019

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“…This chromosomal region is frequently associated with microsatellite instability and loss of heterozygosity (LOH), features frequently associated in the pathogenesis of CRC [6, 7]. Previous studies also reported that low levels of spinophilin expression in tumors are associated with cancer progression and poor prognosis in lung, kidney, head and neck cancer, and leukemia [6, 8]. Ferrer and colleagues demonstrated in mouse embryonic fibroblasts that the loss of spinophilin contributes to high levels of phosphorylated retinoblastoma protein (pRb) with the consequence of increased activation of the tumor suppressor p53 .…”

Section: Introductionmentioning

confidence: 99%

Spinophilin expression determines cellular growth, cancer stemness and 5-flourouracil resistance in colorectal cancer

et al. 2014

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The putative tumor suppressor gene spinophilin has been involved in cancer progression in several types of cancer. In this study, we explored the prognostic value of spinophilin expression in 162 colon adenocarcinoma patients. In addition, we generated stably expressing spinophilin-directed shRNA CRC cell lines and studied the influence of spinophilin expression on cellular phenotypes and molecular interactions. We independently confirmed that low spinophilin expression levels are associated with poor prognosis in CRC patients (p = 0.038). A reduction of spinophilin levels in p53 wild-type HCT116 and p53-mutated Caco-2 cells led to increased cellular growth rates and anchorage-independent growth (p<0.05). At molecular level, reduced spinophilin levels increased the expression of the transcription factor E2F-1. In addition, we observed an increased formation of tumor spheres, increased number of CD133 positive cells and an increased resistance to 5-flourouracil (p<0.05). Finally, treatment with the de-methylating agent 5-aza-dC increased spinophilin expression in CRC cells (p<0.05), corroborated by a correlation of spinophilin expression and extent of methylated CpG sites in the gene promoter region (p<0.001). In conclusion, gain of aggressive biological properties of CRC cells including cellular growth, cancer stem cell features and 5-flourouracil resistance partly explains the role of spinophilin in CRC.

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“…In our own studies, we have explored the role and influence of spinophillin expression in patients with hepatocellular carcinoma (HCC) [4] , head and neck squamous cell carcinoma (HNSCC) [5] and colorectal adenocarcinoma (CRC) [6] . Regarding HNSCC and HCC, our studies were the first to explore the prognostic impact of spinophilin in patients with HNSCC and HCC.…”

Section: Research Highlightmentioning

confidence: 99%

“…It is therefore essential to have a better insight of the oncogenic pathways in order to develop new therapeutic options and improvements in treatment. We evaluated the role of spinophilin and p53 expression by using immunohistochemistry in 85 patients with non-metastatic HNSCC [5] . Reduced levels of spinophilin were observed in 40 tumors (47%) and 9 cases (10.5%) showed a complete loss of spinophilin.…”

Section: Research Highlightmentioning

confidence: 99%

Spinophilin in human cancer – molecular mechanisms and clinical relevance

2015

Can Cell Microenviron

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Loss of the putative tumor suppressor protein spinophilin is associated with poor prognosis in head and neck cancer

Cited by 10 publications

References 14 publications

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Hedgehog pathway proteins SMO and GLI expression as prognostic markers in head and neck squamous cell carcinoma

Spinophilin expression determines cellular growth, cancer stemness and 5-flourouracil resistance in colorectal cancer

Spinophilin in human cancer – molecular mechanisms and clinical relevance

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