Hedgehog signaling pathway molecules and ALDH1A1 expression in early-stage non-small cell lung cancer

Raz, Guy; Allen, Kristi; Kingsley, Chris; Cherni, Irene; Arora, Shilpi; Watanabe, Aprill; Lorenzo, C Di; Edwards, David K.; Sridhar, Shravan; Hostetter, Galen; Weiss, Glen J.

doi:10.1016/j.lungcan.2011.10.015

Cited by 42 publications

(40 citation statements)

References 23 publications

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“…Kendall’s tau-b correlation tests yielded significant correlations between every two factors ( p = 0.000), while Kappa’s test suggested strong positive association between SHh and Gli1( p = 0.000) (Figure 1C), suggesting the canonical Shh pathway is activated in lung SCC. These data are consistent with previous reports that the upstream Shh signaling has correlations with downstream targets in NSCLC [29,30]. Taken together, our results suggest that aberrant activation of the Shh pathway plays an important role in lung SCC.…”

Section: Resultssupporting

confidence: 93%

Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

Yue

Che

et al. 2014

J Exp Clin Cancer Res

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BackgroundSquamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC.MethodsTwo cohorts of patients with lung SCC were studied. Protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. Protein expression levels in tissue specimens were scored and correlations were analyzed. Vismodegib and a Gli inhibitor were used to inhibit Shh/Gli activity, and recombinant Shh proteins were used to stimulate the Hh pathway in lung SCC cell lines. Cell migration assay was performed in vitro.ResultsShh/Gli pathway components were aberrantly expressed in lung SCC tissue samples. Gli1 expression was reversely associated with the expression of EMT markers E-Cadherin and β-Catenin in lung SCC specimens. Inhibition of the Shh/Gli pathway suppressed migration and up-regulated E-Cadherin expression in lung SCC cells. Stimulation of the pathway increased migration and down-regulated E-Cadherin expression in lung SCC cells.ConclusionsOur results suggested that the Shh/Gli pathway may be critical for lung SCC recurrence, metastasis and resistance to chemotherapy. Inhibition of the Shh/Gli pathway activity/function is a potential therapeutic strategy for the treatment of lung SCC patients.

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Section: Resultssupporting

confidence: 93%

Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

Yue

Che

et al. 2014

J Exp Clin Cancer Res

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“…Eberl and colleagues have found that Hh/Gli cooperation with EGRF signaling promotes transformation of and cancer cell progression in vitro [Eberl et al 2012]. In addition, a study conducted by Raz and colleagues examined the correlation between immunohistochemical staining, RDRF and KRAS mutations, and OS [Raz et al 2012]. They found a 6.8% EGRF mutation and no correlation between the pathway proteins and overall survival.…”

Section: Discussionmentioning

confidence: 99%

Sonic hedgehog pathway expression in non-small cell lung cancer

et al. 2012

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Abstract:Objective: Activation of the hedgehog pathway is an important signaling mechanism crucial in embryogenesis and has strong links to carcinogenesis. This study investigates the expression of the Sonic hedgehog pathway molecules in non-small cell lung tumors as it relates to clinical outcome of various non-small cell lung cancers. Methods: A tissue microarray with 81 samples from 42 patients with various non-small cell lung cancer histologies was examined without the aid of laser microdissection. All samples were stained with antibodies directed against Sonic hedgehog, Ptch-1, Smoothened, and Gli-1. Results: Most of the tumor samples showed negative to weak expression of the pathway proteins (Sonic hedgehog, 38% negative to 20% weak; Ptch-1, 100% negative; Smoothened, 69% negative to 7% weak; Gli-1, 57% negative to 5% weak) compared with higher expression in normal lung epithelial cells. Conclusion:The same pathway expression did not correlate with clinical outcome. While our results do not provide any indication that the pathway molecules are correlated to overall patient survival possibly due to the limited sample size, our study shows minimum overexpression of Sonic hedgehog pathway in non-small cell lung cancer and this did not correlate clinically with patient outcome.

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“…Cancer is a major health problem which is responsible for millions of global deaths each year (Raz et al, 2012). It has been estimated that 14.1 million new cases and 8.2 million cancer related death occurred during 2012 (Dosanjh et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Molecular docking study of natural alkaloids as multi-targeted hedgehog pathway inhibitors in cancer stem cell therapy

Mayank

Jaitak

2016

Computational Biology and Chemistry

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Hedgehog signaling pathway molecules and ALDH1A1 expression in early-stage non-small cell lung cancer

Cited by 42 publications

References 23 publications

Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

Sonic hedgehog pathway expression in non-small cell lung cancer

Molecular docking study of natural alkaloids as multi-targeted hedgehog pathway inhibitors in cancer stem cell therapy

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