N-Cadherin Expression Is Associated with Acquisition of EMT Phenotype and with Enhanced Invasion in Erlotinib-Resistant Lung Cancer Cell Lines

Zhang, Xiaoju; Liu, Guang Zhi; Yi, Kang; Dong, Zhaogang; Qian, Qiyu; Ma, Xiaoyan

doi:10.1371/journal.pone.0057692

Cited by 99 publications

(92 citation statements)

References 35 publications

(29 reference statements)

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“…ZNF750 overexpression resulted in decreased expression of the mesenchymal marker N-cadherin. N-cadherin expression is associated with the EMT phenotype and with enhanced invasion in cancer (20). N-cadherin serves an important role in the malignant behaviors of HNSCC (21).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of tumor suppressor gene ZNF750 inhibits oral squamous cell carcinoma metastasis

Yang

Pan

et al. 2017

Oncol Lett

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Abstract. Zinc-finger protein 750 (ZNF750) encodes a putative C2H2 zinc finger protein and is typically mutated or deleted in squamous cell carcinoma. The role of ZNF750 in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the present study was to investigate the effects of ZNF750 overexpression in CAL-27 cells. Cell viability, and the expression of genes associated with proliferation, differentiation and the epithelial-mesenchymal transition were investigated in CAL-27 cells following ZNF750 overexpression, using Cell Counting kit-8, reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. In addition, scratch wound, invasion and migration assays were performed. Cell viability, matrix metalloproteinase 28 expression, cyclin B1 expression and mesenchymal marker neural cadherin expression were decreased following ZNF750 overexpression compared with the control groups. ZNF750 overexpression induced the differentiation-associated genes late cornified envelope 3A and small proline-rich protein 1A and upregulated the expression of late epidermal differentiation factor Kruppel-like factor 4. Overexpression of ZNF750 in CAL-27 cells resulted in inhibition of cell invasion and migration. Taken together, these data suggest that ZNF750 may inhibit the metastasis of OSCC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of tumor suppressor gene ZNF750 inhibits oral squamous cell carcinoma metastasis

Yang

Pan

et al. 2017

Oncol Lett

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“…On the other hand, gradual increases of N-cadherin expression in these breast cancer cell lines were related to EMT-associated mechanisms, regardless of the E-cadherin expression [46], and could be used as stage markers during invasion processes. Furthermore, it has been reported that Ncadherin expression correlates with invasion and motility, plays a direct role in promoting motility, and is involved in EMT and cancer cell metastasis [47]. There are contradictory reports on the effects of estrogen on N-cadherin expression in different cell models; in most cancer cells, it has been shown to negatively regulate N-cadherin induced by the ER signaling pathway [47].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been reported that Ncadherin expression correlates with invasion and motility, plays a direct role in promoting motility, and is involved in EMT and cancer cell metastasis [47]. There are contradictory reports on the effects of estrogen on N-cadherin expression in different cell models; in most cancer cells, it has been shown to negatively regulate N-cadherin induced by the ER signaling pathway [47]. We suggest that high N-cadherin levels initiate EMT but through a different method by which estradiol directly affects breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

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Tumor cells utilize inappropriate epithelialmesenchymal transition (EMT) mechanisms during the invasive process. It is becoming increasingly clear that estradiol (E2) induces breast cancer cell progression and enhances EMT; however, the mechanisms associated with this are unclear. We investigated the role of E2 on the expression and intracellular localization of the tight junction (TJ)-associated proteins, zonula occluden 1 (ZO-1), ZO-1-associated nucleic acid binding (ZONAB), and occludin, on the activation of cSrc and human epidermal growth factor receptor 2 (HER2) expression and cellular migration in the estrogen receptor (ER)-positive breast cancer cell lines, MCF-7 and T47D. WeNovelty and Impact Statements We demonstrated that estrogen is able to induce tight junction (TJ) disruption in two breast cancer cell lines through the activation of c-Src. Ablated expression of the novel epithelial marker CRB3 could lead to increased cell migration. Based on our findings, we propose a novel estrogen-induced TJ pathway associated with breast cancer cell motility and, eventually, to metastasis. demonstrated that 1 nM E2 elicits c-Src activation after 15 min. The p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and increased expression of HER2 mRNAs. These changes correlate with decreased expression of the epithelial markers occludin and CRB3 and increased synthesis of N-cadherin. This led to increased MCF-7 cell migration induced by E2, even in the presence of a cell proliferation inhibitor. Incubation with ICI 182,780 (Fulvestrant), an ER antagonist, precluded the effects of E2 on c-Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, and migration of MCF-7 cells. Our findings suggest that E2 promotes TJ disruption during tumor progression and increases cell motility. We propose a novel pathway where estrogens promote EMTassociated mechanisms that possibly lead to metastasis.

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“…Loss of E-cadherin is considered to be a fundamental event in EMT (27). N-cadherin and vimentin are mesenchymal cell markers, and they are closely related to cell invasion (28,29). In the present study, western blot analysis for E-cadherin, N-cadherin and vimentin protein expression was performed to investigate the effect of ARHI on EMT in colon cancer cells.…”

Section: Discussionmentioning

confidence: 96%

The role of aplysia ras homolog I in colon cancer cell invasion and adhesion

Ouyang

Pan

2017

Exp Ther Med

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Abstract. Aplysia ras homolog I (ARHI) acts as a tumor suppressor in certain cancer cells. However, the role of ARHI in colon cancer development has not previously been reported. The present study aimed to investigate the functional role of ARHI in colon cancer focusing on the aspect of metastasis. Furthermore, the molecular mechanism underlying its function was explored. The present study detected the expression of ARHI in a human colon epithelial cell line and colon cancer cell lines using reverse transcription-quantitative polymerase chain reaction and western blotting analysis. It was demonstrated that ARHI expression was significantly downregulated in colon cancer cell lines compared with the normal colon epithelial cell line (P<0.05). An ARHI-pcDNA3.1 plasmid was transfected into HCT116 cells to overexpress ARHI. The number of invaded cells and the adhesive ability were significantly decreased in the ARHI overexpression group compared with the control group, as determined by cell invasion and adhesion assays (P<0.05). Furthermore, ARHI overexpression led to increased mRNA and protein expression levels of E-cadherin, and decreased mRNA and protein expression levels of N-cadherin and vimentin. Wnt/β-catenin signaling was suppressed in HCT116 cells overexpressing ARHI. Lithium chloride, a wnt/β-catenin signaling activator, was able to attenuate the effect of ARHI on HCT116 cell invasion and adhesion. In addition, the effect of ARHI on epithelial-mesenchymal transition (EMT) in HCT116 cells was reversed by the activation of wnt/β-catenin signaling. In conclusion, the present study provided novel evidence that ARHI could inhibit colon cancer cell invasion and adhesion through suppressing EMT, and these effects were achieved, at least partially, via the suppression of the wnt/β-catenin signaling pathway. The present findings may help in developing novel therapeutic approaches for colon cancer.

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N-Cadherin Expression Is Associated with Acquisition of EMT Phenotype and with Enhanced Invasion in Erlotinib-Resistant Lung Cancer Cell Lines

Cited by 99 publications

References 35 publications

Overexpression of tumor suppressor gene ZNF750 inhibits oral squamous cell carcinoma metastasis

Overexpression of tumor suppressor gene ZNF750 inhibits oral squamous cell carcinoma metastasis

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

The role of aplysia ras homolog I in colon cancer cell invasion and adhesion

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