Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Huang, Niu; Wu, Baogang; Jiang, Hongfang; Li, Hui; Zhang, Yi; Yang, Peng; He, Ping

doi:10.1159/000366396

Cited by 14 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rho signaling governs actin redistribution [32-41] and is implicated in various cellular responses including cell-cell adhesion and EMT [13, 22, 25, 42-45]. In the present work, we reported opposite effects of the KDM2B gene in the expression of RhoA/RhoB/RhoC- and Rac1-GTPases.…”

Section: Discussionsupporting

confidence: 56%

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Zacharopoulou

Tsapara

Kallergi

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. Methods: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins. Results: We report here that KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. On the other hand, KDM2B overexpression downregulated the levels of both epithelial markers and upregulated the mesenchymal marker, suggesting control of EMT by KDM2B. In addition, RhoA, RhoB and RhoC protein levels diminished upon KDM2B-knockdown, while all three small GTPases became upregulated in KDM2B-overexpressing HCT116 cell clones. Interestingly, Rac1 GTPase level increased upon KDM2B-knockdown and diminished in KDM2B-overexpressing HCT116 colon tumor- and DU-145 prostate cancer cells. Conclusions: These results establish a clear functional role of the epigenetic factor KDM2B in the regulation of EMT and small-GTPases expression in colon tumor cells and further support the recently postulated oncogenic role of this histone demethylase in various tumors.

show abstract

Section: Discussionsupporting

confidence: 56%

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Zacharopoulou

Tsapara

Kallergi

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…The study showed that high expression of Rac1 induced EMT in tumor cells in vitro and in vivo 17, 18, and promoted invasion and metastasis of tumor. The inhibition of Rac1 expression significantly up-regulated the expression of E-cadherin, down-regulated the expression of N-cadherin and Vimentin, and significantly inhibited EMT in cancer cells 21. However, the correlation between Rac1 and EMT is still unclear in lung cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

“…As previously described 21, the main criterion of grouping was overall survival, calculated from the date of radiotherapy to the time of death (from any cause). The secondary criterion was local or distant recurrence rate.…”

Section: Methodsmentioning

confidence: 99%

Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer

Zhou¹,

Liao²,

Han³

et al. 2016

J. Cancer

View full text Add to dashboard Cite

Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype.Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed.Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P < 0.05). The aberrant expression of Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P < 0.05). Increased expression of Rac1 may be associated with poor OS and PFS compared with low expression (P<0.001 and P=0.004). Significant correlations were observed between the EMT markers expressed and OS or PFS(P<0.01). In addition, multivariate analysis indicated that the expression of Rac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, P<0.01, respectively) and negatively correlated with E-cad levels (r=-0.464, P<0.001) in NSCLC tissues. Rac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed.Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target.

show abstract

“…Some NSCLCs are resistant to chemotherapy and radiation therapy, and are fast growing and highly invasive [1,2,3,4,5]. Thus, great efforts have been made to elucidate the mechanisms underlying the invasion and chemo-sensitivity of NSCLC [3,4,6,7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

MicroRNA-21 Regulates Non-Small Cell Lung Cancer Cell Invasion and Chemo-Sensitivity through SMAD7

Lin

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: SMAD7 is a key inhibitor of transforming growth factor β (TGFβ) receptor signaling, which regulates the alteration of cancer cell invasiveness through epithelial-mesenchymal cell conversion. Carboplatin is a commonly used drug in the chemotherapy for non-small cell lung cancer (NSCLC). Nevertheless, the molecular mechanisms underlying its suppressive effects on the NSCLC cell invasion are not completely understood. In the current study, we addressed this question by analyzing the effects of Carboplatin on microRNA-regulated SMAD7. Methods: We used Carboplatin to treat NSCLC cell lines. We performed bioinformatics analyses on the binding of microRNA-21 (miR-21) to the 3'-UTR of SMAD7 mRNA, and verified the biological effects of this binding using promoter luciferase reporter assay. The effects of Carboplatin or miR-21-modification on NSCLC cell invasion were evaluated in either a transwell cell invasion assay, or a scratch wound healing assay. Results: We found that Carboplatin inhibited the NSCLC cell invasion, in either a transwell cell invasion assay, or a scratch wound healing assay. Moreover, Carboplatin increased the levels of SMAD7 protein, but not mRNA, in NSCLC cells, suggesting presence of post-transcriptional control of SMAD7 by Carboplatin. Furthermore, expression of miR-21 was found to be inhibited by Carboplatin, and bioinformatics analyses showed that miR-21 targeted the 3'-UTR of SMAD7 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Conclusion: Carboplatin may upregulate SMAD7 through suppression of miR-21 to inhibit TGFβ receptor signaling mediated NSCLC cell invasion.

show abstract

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Cited by 14 publications

References 46 publications

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

The Epigenetic Factor KDM2B Regulates EMT and Small GTPases in Colon Tumor Cells

Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer

MicroRNA-21 Regulates Non-Small Cell Lung Cancer Cell Invasion and Chemo-Sensitivity through SMAD7

Contact Info

Product

Resources

About