Regulation of tumor progression via the Snail‐RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma

Nieh, Shin; Jao, Shu-Wen; Yang, Chin-Yuh; Lin, Yaoh‐Shiang; Tseng, Yi-Han; Liu, Chia‐Lin; Lee, Tsai‐Yu; Liu, Tsung‐Yun; Chu, Yueng‐Hsiang; Chen, Su-Feng

doi:10.1002/hed.23820

Cited by 29 publications

(38 citation statements)

References 41 publications

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“…For the development of efficient therapies against CSCs, it is necessary to isolate and characterize CSCs from tumor tissues or cell lines, and reveal its functional features and stemness maintenance mechanisms. It has been revealed that CD133, CD24, CD105, Snail, Nanog, Twist, OCT-3/4, CRT2, BCL-2,MDR1, KLF4 and so on are stemness markers in CSCs of renal cell carcinoma [13, 16] or other types of tumor [23, 24]. Here, we successfully isolated and characterized the CD133 + /CD24 + subpopulation of RCC ACHN and Caki-1 cell line cells using the magnetic-activated cell sorting (MACS) system and cytometry analysis.…”

Section: Discussionmentioning

confidence: 99%

Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma

Xiao

Gao

Duan

et al. 2017

J Exp Clin Cancer Res

129

107

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BackgroundCancer stem cells (CSCs) are correlated with the initiation, chemoresistance and relapse of tumors. Notch pathway has been reported to function in CSCs maintenance, but whether it is involved in renal cell carcinoma (RCC) CSCs maintaining stemness remain unclear. This study aims to explore the effect of Notch pathway on stemness of CSCs in RCC and the underlying mechanisms.MethodsThe CD133+/CD24+ cells were isolated from RCC ACHN and Caki-1 cell line using Magnetic-activated cell sorting and identified by Flow cytometry analysis. RT-PCR and immunoblot analyses were used for determining the stemness maker expression. The effect of Notch pathway on function of CSCs was assessed by self-renewal ability, chemosensitivity, invasive and migratory ability tumorigenicity in vivo using soft agar colony formation assay, sphere-forming assay, MTT assay, Transwell assay.ResultsHere, we found that the sorted CD133+/CD24+cells possessed elevated stemness maker CTR2, BCL-2, MDR1, OCT-4, KLF4, compared with parental cells, as well as enhanced self-renewal ability, stronger resistance to cisplatin and sorafenib, increased invasion and migration, and higher tumorigenesis in vivo, suggesting the CD133+/CD24+ cells have the stem-like characteristics of CSCs and thus identified as RCC CSCs. Then the enhanced notch1, notch2, Jagged1, Jagged2, DLL1 and DLL4 expression were detected in RCC CSCs and blockage of Notch1 or notch2 using pharmacological inhibitor MRK-003 or its endogenous inhibitor Numb resulted in loss of its stemness features: self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis in vivo. Moreover, it is confirmed that overexpression of notch1 up-regulated CXCR4 inRCC CSCs and augmented SDF-1-induced chemotaxis in RCC CSCs in vitro, which could be rescued when treatment of CXCR4 inhibitor, suggesting that notch signaling promotes the chemotaxis of RCC CSCs by SDF-1/CXCR4 axis.ConclusionsOur results provide a new mechanism of RCC CSCs maintaining stemness via notch pathway as well as a potential therapeutic target in human RCC.

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Section: Discussionmentioning

confidence: 99%

Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma

Xiao

Gao

Duan

et al. 2017

J Exp Clin Cancer Res

129

107

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“…α7 nAChR is the main subtype receptor for tobacco products, and α3 nAChR is another key receptor in oral epithelial cells [31, 32]. The inhibition of α7 nAChR might provide a feasible approach for preventing the progression of head and neck cancer [33]. Previously, we showed that the oral cancer tissues of smokers had higher expression of α3 and α7 nAChR compared with that of non-smokers [34].…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 1 promotes invasion and migration by regulating epithelial-to-mesenchymal transition during oral carcinogenesis

et al. 2016

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Tobacco smoking is the major risk factor for oral squamous cell carcinoma (OSCC). Previously, we found that nicotine up-regulates peroxiredoxin 1 (Prx1), an important antioxidant enzyme, and nuclear factor kappa B (NFκB) in OSCC cells. However, the molecular mechanism of Prx1 in oral carcinogenesis remains obscure. To improve our understanding of the functional role of Prx1 during the cascade of tobacco-associated oral carcinogenesis, we characterized Prx1, NFκB, and epithelial-to-mesenchymal transition (EMT) markers including E-cadherin, vimentin and Snail in 30 primary oral tumors (15 from smokers with OSCC and 15 from non-smokers with OSCC) and 10 normal oral mucosa specimens from healthy individuals. The expression levels of Prx1, nuclear NFκB, vimentin and Snail were higher in the tumors from smokers with OSCC than in those from non-smokers with OSCC or the healthy controls. The expression levels of E-cadherin showed an opposite trend. Prx1 silencing suppressed the nicotine-induced EMT, cell invasion and migration in SCC15 cells in vitro. Furthermore, Prx1 activated the NFκB pathway in SCC15 cells. Prx1 might therefore play an oncogenic role in tobacco-related OSCC and thus serve as a target for chemopreventive and therapeutic interventions.

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“…29,41 Recently, Nieh et al proposed that head and neck squamous cell carcinoma cells express high levels of ABCB1 and ABCG2 in response to increasing Snail levels. 42 Similarly, Saxena et al demonstrated that several ABC transporters contain binding sites for EMT regulators, such as Twist and Snail, and that these factors modulate the promoter activities of ABC transporter genes. 30 On the basis of the aforementioned findings, we investigated whether ALR enhanced the antitumor effect of doxorubicin through the inhibition of the AKT/Snail/MDR-ABC signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Augmenter of liver regeneration potentiates doxorubicin anticancer efficacy by reducing the expression of ABCB1 and ABCG2 in hepatocellular carcinoma

Guo

Jia

et al. 2017

Laboratory Investigation

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Hepatocellular carcinoma (HCC) is highly chemoresistant and therefore challenges both physicians and patients. Augmenter of liver regeneration (ALR), previously also known as 'hepatic stimulator substance', is reported to inhibit the epithelial-mesenchymal transition (EMT) in HCC, one of the frequent events that occur in cancer metastasis, suggesting that ALR is involved in HCC. In this study, we report for the first time that the transfection of ALR enhances the antitumor effect of chemotherapy with doxorubicin, a typical anticancer drug, on HCC in vitro and in vivo. The efflux of doxorubicin from ALR-transfected HCC cells is efficiently suppressed. This implies the intracellular retention of doxorubicin in tumor cells, which is at least partly attributable to the effective inhibition of ABCB1 and ABCG2 transporter expression in ALR-expressing cells. The downregulation of ALR expression by short hairpin RNA diminishes the antitumor effect of ALR. We further demonstrate that ALR inhibits the AKT/Snail signaling pathway, resulting in the downregulation of ABCB1 and ABCG2 expression. In conclusion, our results suggest that ALR is a potential chemotherapeutic agent against HCC.

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Regulation of tumor progression via the Snail‐RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma

Cited by 29 publications

References 41 publications

Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma

Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma

Peroxiredoxin 1 promotes invasion and migration by regulating epithelial-to-mesenchymal transition during oral carcinogenesis

Augmenter of liver regeneration potentiates doxorubicin anticancer efficacy by reducing the expression of ABCB1 and ABCG2 in hepatocellular carcinoma

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