Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer

Xiang, Jiale; Fu, Xiang; Ran, W; Wang, Z

doi:10.1038/oncsis.2016.83

Cited by 74 publications

(64 citation statements)

References 31 publications

(46 reference statements)

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“…EMT has been observed in the majority of tumors (37,38), and emerging evidence also indicates that it may be involved in drug resistance in certain types of cancer cells (7,39), including breast cancer (40,41). In the present study, the observed morphological changes and the upregulation of EMT-related genes in miR-93-overexpressing MCF-7 cells indicated that miR-93 participates in EMT in breast cancer cells.…”

Section: Discussionsupporting

confidence: 58%

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Chu

Xia

et al. 2017

Oncology Reports

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Abstract. It is not well established whether miR-93 is involved in drug resistance and epithelial-mesenchymal transition (EMT) in breast cancer, and its underlying mechanism remains uncertain. In the present study, the expression differences of miR-93 between paired breast cancer tissues confirmed it is involved in the progression of breast cancer. Such a difference was also observed in doxorubicin-resistant and -sensitive cells. Overexpressed miR-93 in sensitive cells revealed increases in cellular proliferation and the expression levels of drug-resistant-related genes, and a decrease in sensitivity to doxorubicin. This demonstrated the relationship between miR-93 and breast cancer drug resistance. Simultaneously, EMT was confirmed in miR-93 overexpressing sensitive cells. This indicated the triadic relationship among miR-93, EMT and drug resistance in breast cancer. We applied the Dual-luciferase Reporter assay to expose the direct interaction between miR-93 and PTEN, which suggested that miR-93 contributes to inducing EMT and drug resistance of breast cancer cells by targeting PTEN.

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Section: Discussionsupporting

confidence: 58%

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Chu

Xia

et al. 2017

Oncology Reports

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“…GRHL2 suppresses EMT and has an expression pattern inversely correlated with that of ZEB1 in numerous cancers (Chen et al, 2016;Chung et al, 2016;Nishino et al, 2017;Paltoglou et al, 2017;Pan et al, 2017;Quan et al, 2014;Werner et al, 2013;Xiang et al, 2017). The miR-200 family of microRNAs, including MIR141, MIR200A, MIR200B, MIR200C and MIR429, along with MIR205, bind to the ZEB1 and ZEB2 mRNAs and inhibit their translation (Gregory et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure

Carpinelli

Vries

Auden

et al. 2020

Disease Models &Amp; Mechanisms

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Cleft lip and palate are common birth defects resulting from failure of the facial processes to fuse during development. The mammalian grainyhead-like (Grhl1-3) genes play key roles in a number of tissue fusion processes including neurulation, epidermal wound healing and eyelid fusion. One family member, Grhl2, is expressed in the epithelial lining of the first pharyngeal arch in mice at embryonic day (E)10.5, prompting analysis of the role of this factor in palatogenesis. Grhl2null mice die at E11.5 with neural tube defects and a cleft face phenotype, precluding analysis of palatal fusion at a later stage of development. However, in the first pharyngeal arch of Grhl2-null embryos, dysregulation of transcription factors that drive epithelialmesenchymal transition (EMT) occurs. The aberrant expression of these genes is associated with a shift in RNA-splicing patterns that favours the generation of mesenchymal isoforms of numerous regulators. Driving the EMT perturbation is loss of expression of the EMT-suppressing transcription factors Ovol1 and Ovol2, which are direct GRHL2 targets. The expression of the miR-200 family of microRNAs, also GRHL2 targets, is similarly reduced, resulting in a 56-fold upregulation of Zeb1 expression, a major driver of mesenchymal cellular identity. The critical role of GRHL2 in mediating cleft palate in Zeb1 −/− mice is evident, with rescue of both palatal and facial fusion seen in Grhl2 −/− ;Zeb1 −/− embryos. These findings highlight the delicate balance between GRHL2/ZEB1 and epithelial/mesenchymal cellular identity that is essential for normal closure of the palate and face. Perturbation of this pathway may underlie cleft palate in some patients.

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“…Given that genetic mutations in hTERT may predispose for IPF (Tsakiri et al, ; Alder et al, ), GRHL2 may be dysregulated in IPF progression. Consistent with its role in lung development, GRHL2 can (a) inhibit EMT‐inducing transcription factor ZEB1 directly, and is inhibited during TGFβ‐mediated EMT (Cieply et al, ; Xiang et al, ), (b) induce epithelial gene expression signature during cancer progression (Xiang et al, ), and (c) maintain collective migration in non–small‐cell lung cancer (NSCLC) H1975 cells that display a stable hybrid E/M phenotype (Jolly et al, ).…”

Section: Emt In Lung Developmentmentioning

confidence: 95%

Epithelial–mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease

Jolly

Ward

Eapen

et al. 2017

Developmental Dynamics

189

146

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Epithelial-mesenchymal transition (EMT) plays key roles during lung development and many lung diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i.e., often cells co-express epithelial and mesenchymal markers but do not fully convert to extracellular matrix (ECM) -producing fibroblasts. Finally, we discuss recent therapeutic attempts to restrict EMT in chronic lung disease. Developmental Dynamics 247:346-358, 2018. V C 2017 Wiley Periodicals, Inc.

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Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer

Cited by 74 publications

References 31 publications

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

miR-93 and PTEN: Key regulators of doxorubicin-resistance and EMT in breast cancer

Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure

Epithelial–mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease

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