Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death

Qiu, Lihua; Di, Wen; Jiang, Qin; Scheffler, Erica; Derby, Steven; Yang, Jian; Kouttab, Nicola; Wanebo, Harold J.; Yan, Bingfang; Wan, Yinsheng

doi:10.3892/ijo.27.5.1441

Cited by 25 publications

(41 citation statements)

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“…Of note, paclitaxel sensitizes EGFR-mediated pathways owing to a transient phosphorylation of EGFR, which is thought to be a potential resistance mechanism of cancer cells to chemotherapy exposure (33,34). Whether dysregulation of the EGFR-mediated pathways precludes or sensitizes cells to paclitaxel therapy is unknown.…”

Section: Discussionmentioning

confidence: 99%

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Schittenhelm

Kollmannsberger

Oechsle

et al. 2009

Molecular Cancer Therapeutics

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Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with nonsmall cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel. This therapy was well tolerated and showed clinical responses in the majority of patients. Although matuzumab displays potent antitumor activity in some patients, not all patients respond well to treatment. Whether dysregulation of EGFR-mediated pathways precludes or sensitizes cells to paclitaxel is unknown. We sought to determine molecular predictive factors for therapy response in a phase

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Section: Discussionmentioning

confidence: 99%

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Schittenhelm

Kollmannsberger

Oechsle

et al. 2009

Molecular Cancer Therapeutics

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“…Moreover, Taxol has been found to be targeting EGFR in CaOV3 cells (18). Exploration of Taxol's molecular targets has aided in the understanding of its pharmacological effects and has also provided experimental data with which its clinical application can be guided.…”

Section: Discussionmentioning

confidence: 99%

“…As previously described (15)(16)(17)(18), treated and untreated cultured cells were washed with cold PBS and harvested by scraping into 150 µl of RIPA buffer with protease inhibitors. Proteins (20-40 µg) were separated by SDS-PAGE and transfered onto PVDF membranes (Millipore, Bedford, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Since EGFR is a significant upstream signal of ACC and EGFR is also activated by Taxol in human ovarian cancer cells (18), the hypothesis that PD and AG were involved in ACC signaling in the presence of Taxol was examined. PD was shown to mediate ACC inhibition, since pretreatment with PD 1 µM for 30 min enhanced Taxol-induced ACC (Fig.…”

Section: Pd (Selective Egfr Inhibitor) and Ag (Selective Egfr Inhibitmentioning

confidence: 99%

“…Numerous studies have shown that over-expression of EGFR is attributed to ovarian cancer cell resistance to Taxol-induced cell death (18,20). Since EGFR is a significant upstream signal of ACC and EGFR is also activated by Taxol in human ovarian cancer cells (18), the hypothesis that PD and AG were involved in ACC signaling in the presence of Taxol was examined.…”

Section: Pd (Selective Egfr Inhibitor) and Ag (Selective Egfr Inhibitmentioning

confidence: 99%

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Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

et al. 2011

Oncology Letters

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Abstract. Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

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Caveolin‐1 contributes to anoikis resistance in human gastric cancer SGC‐7901 cells via regulating Src‐dependent EGFR‐ITGB1 signaling

Wang

Zhu

Mei

et al. 2018

J Biochem & Molecular Tox

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Anoikis resistance is considered to be an essential prerequisite of tumor metastasis and which is an important mechanism in the metastatic process of gastric cancer (GC). Caveolin-1 (CAV-1), a protein component of caveolae, has been reported to regulate several cancer cell behaviors including anoikis resistance. However, the role of CAV-1 in the acquisition of anoikis resistance in GC cells has never been explored. In this study, we investigated the promoting effect of CAV-1 on anchorage-independent growth and anoikis resistance, and the involvement of the related signaling pathways in such process in SGC-7901 cells. The results showed that CAV-1 could promote anchorage-independent growth and anoikis resistance in detached SGC-7901 cells, which was associated with the activation of Src-dependent epidermal growth factor receptor-integrin β signaling as well as the phosphorylation of PI3K/Akt and MEK/ERK signaling pathways. The data from this study might contribute to the in-depth understanding of the metastatic mechanism for GC.

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Targeted inhibition of transient activation of the EGFR-mediated cell survival pathway enhances paclitaxel-induced ovarian cancer cell death

Cited by 25 publications

References 0 publications

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

Caveolin‐1 contributes to anoikis resistance in human gastric cancer SGC‐7901 cells via regulating Src‐dependent EGFR‐ITGB1 signaling

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