Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Lv, Zhuan; Yu, Jane; Zhang, Weijie; Li, Xiong; Wu, Feng; Li, Lifeng; Zhou, Xueliang; Gao, Xiufang; Ding, Xianfei; Liang, Han; Yafei, Cai; Ma, Wei; Wang, Liuxing

doi:10.18632/oncotarget.15624

Cited by 11 publications

(7 citation statements)

References 52 publications

(55 reference statements)

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“…As previously reported, LGR5 can promote the invasion and migration of colorectal cancer ( 16 ), esophageal squamous cell carcinoma ( 20 ) and gastric cancer ( 21 ). To further confirm the role of LGR5 in NSCLC cell migration, we performed a wound-healing assay with LGR5-transfected and Mock-transfected NSCLC cells.…”

Section: Resultssupporting

confidence: 55%

The biological functions of LGR5 in promoting non-small cell lung cancer progression

Gao¹,

Xu²,

You³

et al. 2019

Transl. Cancer Res

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Background The Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), which is used as a marker of adult stem cells and colorectal cancer stem cells (CSCs), is closely associated with the progression of non-small cell lung cancer (NSCLC). This study aimed to identify the clinical significance and biological function of LGR5 in NSCLC. Methods Quantitative reverse transcription polymerase chain reaction (RT-PCR) was applied to detect the expression of LGR5 and stemness-related genes in 22 NSCLC patients, and the clinical significance of LGR5 in NSCLC progression was estimated by statistical analysis. LGR5 overexpressing A549- and H1299-transfected cells were established, and CCK-8 and clone formation assays were used to test the proliferation ability. A wound-healing assay was utilized to clarify the migration ability. The invasion ability was confirmed via the Transwell assay kit. Results LGR5 expression was markedly higher in NSCLC tissues than in the matched adjacent normal tissues, and had a trend to associate with tumor size, lymph node metastasis, and TNM stage. The proliferation rates, clone formation rates, wound healing rates, number of invasive cells, and the NOTCH1 expression of the LGR5 overexpressing groups, were significantly higher than those of the control groups. Conclusions LGR5 plays an essential role in NSCLC tumorigenesis and is closely associated with the proliferation, metastasis, and invasion of NSCLC cells. LGR5 may promote NSCLC progression via NOTCH1 and could be a new target for gene-targeted therapies for NSCLC.

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Section: Resultssupporting

confidence: 55%

The biological functions of LGR5 in promoting non-small cell lung cancer progression

Gao¹,

Xu²,

You³

et al. 2019

Transl. Cancer Res

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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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“…161 Lgr5, a member of the G proteincoupled receptor (GPCR) family of proteins, is located downstream of the Wnt signaling pathway and restrains the differentiation of esophageal SCC stem cells. 162 Wnt signaling also plays an important role in regulating CSC apoptosis. Dickkopf-related protein 2 induces G0/G1 arrest and cell apoptosis by suppressing β-catenin activity in breast CSCs.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,212

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Cited by 11 publications

References 52 publications

The biological functions of LGR5 in promoting non-small cell lung cancer progression

The biological functions of LGR5 in promoting non-small cell lung cancer progression

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

Targeting cancer stem cell pathways for cancer therapy

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