Inhibition of Apoptosis by Amphiregulin via an Insulin-like Growth Factor-1 Receptor-dependent Pathway in Non-small Cell Lung Cancer Cell Lines

Hurbin, Amandine; Dubrez, Laurence; Coll, Jean‐Luc; Favrot, Marie‐Christine

doi:10.1074/jbc.m207584200

Cited by 87 publications

(58 citation statements)

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“…We have previously shown that in H358 CM obtained from serum-free medium cell culture, IGF1 level was about 1 ng/ml, as usually observed in CM of other analyzed cancer cell lines, but the AR level was very high: 5 ng/ml, 50 more than in CM from other analyzed cancer cell lines (11). In all experiments performed in this paper, levels of AR and IGF1 in H358 CM were controlled as described (11) and shown to be similar.…”

Section: Methodsmentioning

confidence: 99%

“…In all experiments performed in this paper, levels of AR and IGF1 in H358 CM were controlled as described (11) and shown to be similar.…”

Section: Methodsmentioning

confidence: 99%

“…1) H358 cells secrete AR and IGF1 that cooperate to inhibit apoptosis induced by serum deprivation in an autocrine manner (11). Those two factors also protect H322 cells from apoptosis in a paracrine manner when cells are incubated with conditioned medium from H358 cells (CM) or with the two growth factors at concentrations found in the H358 CM (11). 2) AR inhibits apoptosis through an IGF1-dependent survival pathway, independently of the EGF receptor (11).…”

mentioning

confidence: 99%

“…Those two factors also protect H322 cells from apoptosis in a paracrine manner when cells are incubated with conditioned medium from H358 cells (CM) or with the two growth factors at concentrations found in the H358 CM (11). 2) AR inhibits apoptosis through an IGF1-dependent survival pathway, independently of the EGF receptor (11). 3) H358 cells resist to Bax-induced apoptosis through an inactivation of Bax conformational change (12).…”

mentioning

confidence: 99%

“…Moreover, we have previously shown the following, on two NSCLC cell lines, H322 and H358. 1) H358 cells secrete AR and IGF1 that cooperate to inhibit apoptosis induced by serum deprivation in an autocrine manner (11). Those two factors also protect H322 cells from apoptosis in a paracrine manner when cells are incubated with conditioned medium from H358 cells (CM) or with the two growth factors at concentrations found in the H358 CM (11).…”

mentioning

confidence: 99%

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Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells

Hurbin

Coll

Dubrez

et al. 2005

Journal of Biological Chemistry

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Amphiregulin (AR) and insulin-like growth factor-1 (IGF1) are growth factors known to promote non-small cell lung cancer (NSCLC) survival. We have previously published that 1) AR and IGF1, secreted by H358 NSCLC cells, cooperate to protect those cells and H322 NSCLC cells from serum-starved apoptosis; 2) H358 cells resist Bax-induced apoptosis through an inhibition of Bax conformational change. We show here that the antiapoptotic activity of the AR/IGF1 combination is specifically abolished by the PKC inhibitors calphostin C and staurosporine, but not by the MAPK and phosphatidylinositol 3-kinase inhibitors PD98059 and wortmannin, suggesting the involvement of a PKC-dependent and MAPKand phosphatidylinositol 3-kinase-independent survival pathway. The PKC␦ inhibitor rottlerin restores apoptosis induced by serum deprivation. In addition, phosphorylation of PKC␦ and PKC/, but not of PKC␣/␤ II , increases in serum-starved H358 cells and in H322 cells treated with an AR/IGF1 combination and is blocked by calphostin C. The combination of AR and IGF1 increases p90 rsk and Bad phosphorylation as well as inhibiting the conformational change of Bax by a PKC-dependent mechanism. Finally, PKC␦, PKC, or p90 rsk small interfering RNAs block the antiapoptotic activity of AR/IGF1 combination but have no effect on partial apoptosis inhibition observed with each factor used alone. Constitutively active PKC expression inhibits serum deprivation-induced apoptosis, whereas a catalytically inactive form of p90 rsk restores it. Thus, AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90 rskdependent pathway, which leads to Bad and Bax inactivation. This signaling pathway is different to that used by single factor.

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Section: Methodsmentioning

confidence: 99%

“…In all experiments performed in this paper, levels of AR and IGF1 in H358 CM were controlled as described (11) and shown to be similar.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells

Hurbin

Coll

Dubrez

et al. 2005

Journal of Biological Chemistry

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EGFR inhibition in the treatment of non‐small cell lung cancer

Gerber

2008

Drug Development Research

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Epidermal growth factor receptor (EGFR) inhibitors have introduced the concept of targeted therapy to the treatment of non-small cell lung cancer (NSCLC). These agents appear most effective in patients with tumors that are highly dependent on EGFR signaling pathways, a population that disproportionately includes females, nonsmokers, individuals of East Asian origin, and patients with adenocarcinoma histology. Currently available EGFR-inhibiting drugs include the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, and lapatinib, which are administered orally and interfere with the intracellular tyrosine kinase domain, and the monoclonal antibodies (mAbs) cetuximab and panitumumab, which are administered intravenously and interfere with extracellular ligand binding. While the use of EGFR TKIs as monotherapy prolongs survival in metastatic NSCLC, they have demonstrated no benefit when added to conventional, cytotoxic chemotherapy. In contrast, the anti-EGFR mAb cetuximab appears most effective when combined with chemotherapy or radiation. Despite dramatic initial responses to treatment in some cases, NSCLC eventually becomes resistant to EGFR inhibition. Possible mechanisms include secondary mutations that interfere with drug binding, oncogenic pathways driven by other receptor tyrosine kinases, and independent activity of downstream signaling molecules. Efforts to overcome such resistance include irreversibly binding EGFR TKIs, multi-targeted TKIs, and combinations with chemotherapy, radiation, and other targeted therapies.

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Impact of IGF‐1R/EGFR cross‐talks on hepatoma cell sensitivity to gefitinib

Desbois-Mouthon

Cacheux

Eggelpoël

et al. 2006

Intl Journal of Cancer

109

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Epidermal growth factor receptor (EGFR)-and type 1 insulin-like growth factor receptor (IGF-1R)-dependent pathways are upregulated in hepatocellular carcinoma (HCC), and cross-talks between both pathways have been described in other systems. Gefitinib, a specific EGFR inhibitor, has shown to reduce significantly, although not completely, HCC formation in rat cirrhotic liver. Here, we investigated whether IGF-1R-dependent pathways may interfere with EGFR signalling in hepatoma cells and, if so, whether such cross-talks may affect the antitumoral effect of gefitinib in these cells. We show that the proliferative action of IGF2 in HepG2 and Hep3B cells requires EGFR activation through the autocrine/paracrine release of amphiregulin. Thus, IGF2-induced extracellular signal-regulated kinase activity and DNA synthesis were inhibited by neutralizing antibodies against either EGFR or amphiregulin and by TAPI-1, a pharmalogical inhibitor of tumor necrosis factor-a converting enzyme, a sheddase of amphiregulin. Accordingly, IGF2 and EGF stimulating effects on cell proliferation were both strongly repressed by gefitinib. However, while gefitinib blocked Akt activation by EGF, it had no effect on Akt activation by IGF2 and did not cause apoptosis by its own. AG1024, a selective IGF-1R inhibitor, induced apoptosis and this effect was potentiated by gefitinib. In conclusion, we show that in HCC cells IGF2/IGF-1R activation triggers proliferative and survival signals through EGFR-dependent and -independent mechanisms, respectively. The IGF2/IGF-1R survival pathway may contribute to gefitinib resistance in these cells. Therefore, the inhibition of IGF2/IGF-1R signalling could potentiate the anti-tumoral effect of gefinitib in HCC. ' 2006 Wiley-Liss, Inc.

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Inhibition of Apoptosis by Amphiregulin via an Insulin-like Growth Factor-1 Receptor-dependent Pathway in Non-small Cell Lung Cancer Cell Lines

Cited by 87 publications

References 54 publications

Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells

Cooperation of Amphiregulin and Insulin-like Growth Factor-1 Inhibits Bax- and Bad-mediated Apoptosis via a Protein Kinase C-dependent Pathway in Non-small Cell Lung Cancer Cells

EGFR inhibition in the treatment of non‐small cell lung cancer

Impact of IGF‐1R/EGFR cross‐talks on hepatoma cell sensitivity to gefitinib

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