ABL Regulation by AXL Promotes Cisplatin Resistance in Esophageal Cancer

Hong, Jun; Peng, Dun Fa; Chen, Zheng; Sehdev, Vikas; Belkhiri, Abbes

doi:10.1158/0008-5472.can-12-3151

Cited by 77 publications

(71 citation statements)

References 30 publications

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“…E1A downregulates the expression of AXL, and this phenomenon is correlated with chemosensitization and the poor prognosis of patients with breast cancer (30,31). Therefore, we wondered whether AXL is involved in Dicer-regulated chemosensitization and cancer stem cell properties.…”

Section: Resultsmentioning

confidence: 99%

Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL

et al. 2016

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Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity. We found that Dicer expression was regulated at the transcription level by E1A, through activation of an MAPK14/CEBPa pathway. Our findings define a mechanism of E1A-mediated chemosensitization for paclitaxel, which is based upon the suppression of breast cancer stem-like cells, with potential implications for the diagnosis and treatment of breast cancer patients. Cancer Res; 76(13); 3916-28. Ó2016 AACR.

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Section: Resultsmentioning

confidence: 99%

Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL

et al. 2016

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“…AXL is also implicated in angiogenesis (61) and immune response (62). Preclinical findings and retrospective studies have illustrated that overexpression of AEG-1 and AXL confers broad drug resistance to chemotherapeutic agents, including paclitaxel (63), cisplatin (64,65) and 5-FU (27). However, no correlations were observed in the present study between AEG-1 and AXL mRNA expression levels and patients' outcome to chemotherapy, either in first-line or second-line chemotherapy.…”

Section: Discussioncontrasting

confidence: 70%

High BIM mRNA levels are associated with longer survival in advanced gastric cancer

Huang

Zou

et al. 2017

Oncology Letters

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Abstract. Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed (r s =0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.

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“…Upregulated in many forms of cancer (6), AXL overexpression has been linked to metastasis (7,8), poor survival (9)(10)(11), and drug resistance (12,13). Critically, AXL-deficient mice have mild phenotypes (14), suggesting complete abrogation of signaling through the AXL receptor would confer minimal on-target toxicity.…”

Section: Introductionmentioning

confidence: 99%