Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway

Ji, Chao; Yang, Lang; Yi, Weijing; Xiang, Dongfang; Wang, Yanxia; Zhou, Zhihua; Qian, Feng; Ren, Yong; Cui, Wei; Zhang, Xia; Zhang, Peng; Wang, Ji Ming; Cui, You‐Hong; Bian, Xiu‐Wu

doi:10.1038/s41388-018-0226-z

Cited by 37 publications

(32 citation statements)

References 65 publications

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“…GC stem-like cells have been suggested to accelerate the refractory properties of GC, with uncontrolled self-renewal, and tumor-initiating abilities [5]. A growing body of studies have intended to delineate the regulatory mechanisms in GC stemlike cells and to identify strategies targeting GC stem-like cells, in an attempt to curtail the metastasis and recurrence of GC [6,7]. Accumulating evidence has identified molecular pathways, such as cell growth, apoptosis, angiogenesis, and invasion, for potential molecular therapeutic targets for the treatment of GC [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1

Yan

Wei

et al. 2019

Cell Cycle

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Emerging evidence has identified the critical role of microRNAs in gastric cancer (GC). Herein, this study intends to characterize the tumor suppressive role of microRNA-598 (miR-598) in GC stemlike cells, with the involvement of RRS1. The CD133+ GC stem-like cells were sorted by flow cytometry, after which immunofluorescence assay was used to determine the co-localization of CD133 and CD44v8-10. The miR-598 expression was examined in the CD133+ and CD133-cells. Subsequently, the CD133+ cells were subjected to miR-598 mimics, miR-598 inhibitors or RRS1 siRNA to validate the effect of miR-598 on GC stem-like cell proliferation, colony formation, apoptosis, migration and invasion capacities. Besides, the effect of miR-598 on the expression of key factors (OCT4, SOX2 and NANOG) associated with stem cell characteristics was measured. The obtained results indicated that the sphere forming capacity was higher in CD133+ cells. CD133 + MKN-45 cells expressed CD133 and CD44v8-10, and were expressed on the cell membrane. MiR-598 was poorly expressed in CD133+ cells. Notably, miR-598 negatively regulated RRS1. In response to miR-598 mimics and RRS1 siRNA, the MKN-45 cells displayed inhibited proliferation, colony formation, migration and invasion, accompanied by elevated apoptosis. Besides, the miR-598 inhibitors reversed the situation. This study highlights that miR-598 a tumor suppressor in GC stem-like cells by inhibiting RRS1, whereby miR-598 represses MKN-45 cell growth and invasion by attenuating self-renewal of GC stem-like cells.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1

Yan

Wei

et al. 2019

Cell Cycle

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“…Among those differentially expressed gene coregulated by EGFR and PKM2, FOSL1, and ANTXR2 are recently suspected to promote cancer progression ( 38 , 39 ). Western blot analysis showed that FOSL1 and ANTXR2 protein levels are downregulated in EGFR- or PKM2-silenced NPC cells ( Figure 6A ).…”

Section: Resultsmentioning

confidence: 99%

EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2

et al. 2019

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Abstract Nasopharyngeal carcinoma (NPC) is notorious for its aggressiveness and high metastatic potential. NPC patients with distant metastasis have a particularly poor prognosis; however, evaluating metastatic potential by expression profiles of primary tumors is challenging. This study aimed to investigate the association between activation of epidermal growth factor receptor (EGFR) signaling and NPC metastasis and the underlying mechanisms. We found an association between EGFR protein overexpression and intense EGFR immunostaining in NPC samples with advanced tumor node metastasis stage, clinical stage, and distant metastasis in NPC patients. Exogenous EGF stimulates NPC mobility and invasiveness in vitro. Activation of EGFR signaling prompted PKM2 translocation to the nucleus. Silencing either EGFR or PKM2 attenuates NPC cell aggressiveness in vitro and in vivo. Blocking EGFR signaling with cetuximab suppressed NPC cell invasiveness in vitro and metastatic potential in vivo. Comprehensive analyses of transcriptome profiles indicated that the EGFR-PKM2 axis activates a number of novel metastasis promoters, including F3, FOSL1, EPHA2, ANTXR2, and AKR1C2. Finally, we found that the metastasis-promoting function of the EGFR-PKM2 axis is dependent on nuclear PKM2 regulation of the transcription of metastasis-related genes, including FOSL1 and ANTXR2. Our study indicates that EGFR-PKM2 signaling promotes NPC cell invasion and metastasis through induction of FOSL1 and ANTXR2 and identifies EGFR as a promising biomarker for predicting the risk of distant metastasis.

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“…Some proteins (DKK2 (Dickkopf-related protein 2), DACT1, CDH11, GECG, PKM2, EZH2, CD44v6, MYC, and TERT), microRNAs (miR-1246, miR-9, miR-92a, miR-544a, and miR-483-5p), and long noncoding RNAs (lncR-β-catm and lncR-TCF7) regulate the activation of the Wnt/β-catenin pathway in CSCs prostate CSCs. 141 Capillary morphogenesis gene 2 increases the expression of nuclear β-catenin to regulate the self-renewal and tumorigenicity of gastric CSCs, 151 and SMYD3, which is located downstream of the Wnt pathway, has a similar effect. 152 In addition, long noncoding RNAs and microRNAs also promote selfrenewal of CSCs through the Wnt signaling pathway.…”

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

1,233

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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Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway

Cited by 37 publications

References 65 publications

RETRACTED ARTICLE: MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1

RETRACTED ARTICLE: MicroRNA-598 inhibits the growth and maintenance of gastric cancer stem-like cells by down-regulating RRS1

EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2

Targeting cancer stem cell pathways for cancer therapy

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