Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

Carrasco‐García, Estefanía; Saceda, Miguel; Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gómez-Martínez, Ángeles; García-Morales, Pilar; Ferragut, José A.; Martínez-Lacaci, Isabel

doi:10.1016/j.yexcr.2011.03.015

Cited by 49 publications

(35 citation statements)

References 47 publications

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“…Indeed, ERK1/2 activation was inhibited by erlotinib but not by the antibody. Our data are in agreement with the report of Carrasco-Garcia and colleagues (33), in which they have compared the antiproliferative effects of small-molecule inhibitors of EGFR (AG1478, erlotinib) and cetuximab (the clinically used anti-EGFR antibody) on glioblastoma cell proliferation. This study demonstrated that EGFR TKIs are able to sustain the inactivation of ERK1/2, whereas cetuximab did not.…”

Section: Discussionsupporting

confidence: 93%

“…Erlotinib antiproliferative effect on MDA-MB-231 cells expressing or not MT4-MMP was more efficient than AG1478. Structurally, erlotinib and AG1478 share the same structural quinazole backbone but AG1478 lacks the hydrophylique side chains that may confer different properties to erlotinib (33). Erlotinib inhibited also the MT4-MMP-mediated proliferation in BT549 cells and has a slight effect on control cells (Fig.…”

Section: Mt4-mmp Exerts Its Mitogenic Effect Through Egfr Signalingmentioning

confidence: 98%

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EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

et al. 2014

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MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol-anchored matrix metalloprotease expressed on the surface of cancer cells that promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGFa and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expressions were correlated in human triple-negative breast cancer specimens. Altogether, our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. Cancer Res; 74(23); 6758-70. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 93%

Section: Mt4-mmp Exerts Its Mitogenic Effect Through Egfr Signalingmentioning

confidence: 98%

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

et al. 2014

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“…In this article, we used T98G and U87 cells and EFGR status is wild-type in U87 cells and the expression level of STAT3 was low. In T98G cells, EGFR is known to be amplified and STAT3 was highly expressed (47). In case of PTEN, both U87 and T98G have been shown to be mutated (48).…”

Section: Discussionmentioning

confidence: 99%

STAT3 Inhibition Overcomes Temozolomide Resistance in Glioblastoma by Downregulating MGMT Expression

Wang

Yachi

Mahabir

et al. 2012

Molecular Cancer Therapeutics

171

139

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Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with a poor prognosis. Current standard treatment includes chemotherapy with the DNA-alkylating agent temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide-induced DNA damage due to elevated expression of the DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT). Here, we show that upregulation of both MGMT and STAT3 was accompanied with acquisition of temozolomide resistance in the GBM cell line U87. Inactivation of STAT3 by inhibitor or short hairpin RNA (shRNA) downregulated MGMT expression in GBM cell lines. MGMT upregulation was not observed by the treatment of interleukin (IL)-6 which is a strong activator of STAT3. Contrarily, forced expressed MGMT could be downregulated by STAT3 inhibitor which was partially rescued by the proteasome inhibitor, MG132, suggesting the STAT3-mediated posttranscriptional regulation of the protein levels of MGMT. Immunohistochemical analysis of 44 malignant glioma specimens showed significant positive correlation between expression levels of MGMT and phosphorylated STAT3 (p-STAT3; P < 0.001, r ¼ 0.58). Importantly, the levels of both MGMT and p-STAT3 were increased in the recurrence compared with the primary lesion in paired identical tumors of 12 cases. Finally, we showed that STAT3 inhibitor or STAT3 knockdown potentiated temozolomide efficacy in temozolomide-resistant GBM cell lines. Therefore, STAT3 inhibitor might be one of the candidate reagents for combination therapy with temozolomide for patients with temozolomide-resistant GBM.

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“…Cell cycle analysis was carried out essentially as previously described (Carrasco-García et al 2011). Briefly, for cell cycle distribution of DNA content, control and cells treated with the different phenolics were trypsinized, washed with PBS, and fixed with 75 % cold ethanol at -20°C for at least 1 h. Then, cells were incubated with 0.5 Triton X-100 and 25 lg/mL RNase A in PBS, stained with 25 ng/mL propidium iodide, incubated for 30 min in the dark, and analyzed using an Epics XL flow cytometer equipped with a 0.75 W argon laser set at 488 nm (Beckman Coulter Co., Miami, FL).…”

Section: Cell Cycle Studymentioning

confidence: 99%

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

et al. 2012

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In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obtained from microarray analysis. Reverse transcription quantitative-PCR was used to confirm relative changes in mRNA levels of selected genes from microarrays. The selection of genes was based on their expression change, adjusted p value, and known biological function. According to genome-wide transcriptomics analysis, rosemary polyphenols altered the expression of *4 % of the genes covered by the Affymetrix Human Gene 1.0ST chip in both colon cancer cells. However, only *18 % of the differentially expressed genes were common to both cell lines, indicating markedly different expression profiles in response to the treatment. Differences in induction of G2/ M arrest observed by rosemary polyphenols in the two colon adenocarcinoma cell lines suggest that the extract may be differentially effective against tumors with specific mutational pattern. From our results, it is also concluded that rosemary polyphenols induced a low degree of apoptosis indicating that other multiple signaling pathways may contribute to colon cancer cell death.

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Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

Cited by 49 publications

References 47 publications

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

STAT3 Inhibition Overcomes Temozolomide Resistance in Glioblastoma by Downregulating MGMT Expression

Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis

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