J Cancer 2016; 7(12):1579-1586. doi:10.7150/jca.14713 This issue Cite

Research Paper

AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells

Sherif Abdelhamed, Keisuke Ogura, Satoru Yokoyama, Ikuo Saiki, Yoshihiro Hayakawa

Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Sugitani, Toyama, Japan.

Citation:
Abdelhamed S, Ogura K, Yokoyama S, Saiki I, Hayakawa Y. AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells. J Cancer 2016; 7(12):1579-1586. doi:10.7150/jca.14713. https://www.jcancer.org/v07p1579.htm
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Abstract

While cancer development and progression can be controlled by cytotoxic T cells, it is also known that tumor-specific CD8+T cells become functionally impaired by acquiring a group of inhibitory receptors known as immune checkpoints. Amongst those, programmed death-1 (PD-1) is one of the most recognized negative regulators of T cell function. In non-small lung cancers (NSCLCs), the aberrant activation of epidermal growth factor receptor (EGFR) is known to induce PD-L1 expression and further the treatment with gefitinib, a tyrosine kinase inhibitor (TKI) for EGFR, decrease the expression of PD-L1 on NSCLC. Given the acquired resistance to gefitinib treatment frequently observed by developing secondary-site mutations limiting its efficacy, it is important to understand the downstream mechanism of activated-EGFR signaling for regulating PD-L1 in NSCLC. In this study, we demonstrated that AKT-STAT3 pathway could be a potential target for regulating the surface expression of PD-L1 on NSCLCs with aberrant EGFR activity and, further, the inhibition of AKT or STAT3 activity could down-regulate the expression of PD-L1 even in gefitinib-resistant NSCLCs. These results highlight an importance of AKT-STAT3 pathway as a promising target for potentiating anti-tumor immune responses by regulating PD-L1 expression on cancer cells with aberrant EGFR activity.

Keywords: non-small lung cancer, EGFR, AKT, STAT3, PD-L1


Citation styles

APA
Abdelhamed, S., Ogura, K., Yokoyama, S., Saiki, I., Hayakawa, Y. (2016). AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells. Journal of Cancer, 7(12), 1579-1586. https://doi.org/10.7150/jca.14713.

ACS
Abdelhamed, S.; Ogura, K.; Yokoyama, S.; Saiki, I.; Hayakawa, Y. AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells. J. Cancer 2016, 7 (12), 1579-1586. DOI: 10.7150/jca.14713.

NLM
Abdelhamed S, Ogura K, Yokoyama S, Saiki I, Hayakawa Y. AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells. J Cancer 2016; 7(12):1579-1586. doi:10.7150/jca.14713. https://www.jcancer.org/v07p1579.htm

CSE
Abdelhamed S, Ogura K, Yokoyama S, Saiki I, Hayakawa Y. 2016. AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells. J Cancer. 7(12):1579-1586.

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