Correction: LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma

Vieira, Gabriella Cunha; Chockalingam, Sreekumar; Melegh, Zsombor; Greenhough, Alexander; Malik, Sally; Szemes, Marianna; Park, Ji Hyun; Kaidi, Abderrahmane; Zhou, Li; Catchpoole, Daniel; Morgan, Rhys G.; Bates, David O.; Gabb, Peter J.; Malik, Karim

doi:10.18632/oncotarget.17685

Cited by 3 publications

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“…Reports have shown that the CSC marker, EpCAM, may be successfully used as a tumor marker in gastric, ovarian, and breast cancer because its high expression in these cancers is closely related to tumor growth, metastasis and advanced tumor stage (30)(31)(32). Similarly, increased expression of LGR5 in esophageal cancer and neuroblastoma can enhance tumor cell invasion and migration (33,34). Moreover, studies are underway to determine the relationship between LGR5 and PTC (35).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

Wang

Lin

et al. 2018

Oncol Rep

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Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer in vitro using patient tissue samples and a panel of thyroid cancer cell lines, and in vivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the expression of cancer stem cell markers LGR5 and EpCAM via the c-Raf/MEK/ERK signaling pathway. Therefore, BANCR may be used as a novel prognostic marker for PTC.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

Wang

Lin

et al. 2018

Oncol Rep

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“…These tumor-spheres exhibited high expression of Wnt target genes and higher in vivo tumorigenicity (Coulon et al, 2011). Moreover, Vieira et al (2017) demonstrated the important role of LRG5 in regulating NB survival and proliferation via the MEK/ERK-Wnt/β-Catenin signaling pathways. In fact, MEK/ERK activity has been implicated in the maintenance of embryonic stem cells in the undifferentiated state as well as CSCs in glioma (Kwon et al, 2017), breast cancer (Baker et al, 2018), thyroid cancer (Wang K. et al, 2018), lung cancer (Ning et al, 2018), gastric cancer (Ning et al, 2018), glioblastoma (Wang F. et al, 2018) and rhabdomyosarcoma (Ciccarelli et al, 2016).…”

Section: Neuroblastoma Cancer Stem Cells: From Genes To Therapiesmentioning

confidence: 99%

“…This stem cell marker was found to be overexpressed in several types of cancers, such as glioblastoma (Nakata et al, 2013), cervical (Cao et al, 2017), breast (Yang et al, 2015) and colorectal cancers (Hirsch et al, 2014; Yanai et al, 2017). In addition, LGR5 was found to be overexpressed in high grade NB (Forgham et al, 2015; Vieira et al, 2017), working upstream of the MEK/ERK and Akt pro-survival signaling pathways (Vieira et al, 2017) which are often triggered in primary NB tumors (Opel et al, 2007).…”

Section: Bmi1mentioning

confidence: 99%

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier

Bahmad

Chamaa

Assi

et al. 2019

Front. Mol. Neurosci.

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Neuroblastoma (NB) is the most common extracranial solid tumor often diagnosed in childhood. Despite intense efforts to develop a successful treatment, current available therapies are still challenged by high rates of resistance, recurrence and progression, most notably in advanced cases and highly malignant tumors. Emerging evidence proposes that this might be due to a subpopulation of cancer stem cells (CSCs) or tumor-initiating cells (TICs) found in the bulk of the tumor. Therefore, the development of more targeted therapy is highly dependent on the identification of the molecular signatures and genetic aberrations characteristic to this subpopulation of cells. This review aims at providing an overview of the key molecular players involved in NB CSCs and focuses on the experimental evidence from NB cell lines, patient-derived xenografts and primary tumors. It also provides some novel approaches of targeting multiple drivers governing the stemness of CSCs to achieve better anti-tumor effects than the currently used therapeutic agents.

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“…For instance, deletion of APC in LGR5-positive cells was related to the development of intestinal adenomas ( 5 ). LGR5 has also been shown to be diffusely overexpressed in colonic adenomas and adenocarcinomas and a range of other gastrointestinal and nongastrointestinal malignancies ( 10 – 16 ). These data raise the additional possibility that LGR5 expression in Barrett's epithelium may help predict progression to advanced neoplasia.…”

Section: Introductionmentioning

confidence: 99%

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia

Neyaz

Odze

Rickelt

et al. 2020

Clin Transl Gastroenterol

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INTRODUCTION: The expression of LGR5, a known stem cell marker, is poorly understood in Barrett's esophagus (BE) and related neoplasia. The aim of this study was to evaluate LGR5 in BE and related neoplasia and to evaluate its utility as a potential biomarker of progression to advanced neoplasia. METHODS: We evaluated total 137 patients, including 119 with BE and 18 with normal gastroesophageal mucosa for expression of LGR5 using RNA in situ hybridization; this also included 28 progressors and 30 nonprogressors. The LGR5 stain was evaluated using 1 qualitative and 2 quantitative parameters, using manual and automated platforms. RESULTS: Surface LGR5 expression was mainly seen in high-grade dysplasia (12/18) compared with low-grade dysplasia (1/8) and nondysplastic BE (0/17) ( P < 0.0001). In contrast to nondysplastic BE, low- and high-grade dysplasia showed a higher percentage of mean number of LGR5-positive crypts per patient ( P < 0.0001) and an increase in the mean number of LGR5 transcripts per cell ( P < 0.0001). The mean percentage of LGR5-positive crypts per patient and the mean number of LGR5 transcripts per cell were also significantly higher in nondysplastic BE from progressor compared with nonprogressor ( P < 0.0001, P = 0.014). The sensitivity and specificity of LGR5 for distinguishing progressor from nonprogressor were 50% and 87%, respectively. DISCUSSION: BE-related advanced neoplasia shows an expansion of the LGR5-positive cellular compartment, supporting its role as a stem cell marker in this disease. Quantitative LGR5 expression and surface epithelial reactivity are novel biomarkers of increased risk of progression to advanced neoplasia in BE.

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Correction: LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma

Abstract: Figure 5:LGR5 regulates MEK/ERK and Akt signalling. Immunoblotting demonstrating A. decreases in p-ERK1/2 (T202/Y204) and p-MEK1/2 (S217/221), B. Elevated Bim-EL and C. altered Akt phosphorylation and Rictor levels accompanying LGR5 knockdown.

Cited by 3 publications

References 0 publications

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia

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