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. Author manuscript; available in PMC: 2019 Jul 1.
Published in final edited form as: Lung Cancer. 2018 May 1;121:82–90. doi: 10.1016/j.lungcan.2018.04.024

Fig. 6. Proposed model of functional cooperation between HIF-1α and c-Jun in regulating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR.

Fig. 6

HIF-1α and c-Jun are upregulated or phosphorylated by cell signal pathways downstream of EGFR and by environmental cues. Both HIF-1 and AP-1 activate transcription of target genes. AP-1 enhances c-Jun expression through a positive feed-forward loop. c-Jun upregulation prevents HIF-1α ubiquitination and degradation. HIF-1 may upregulate c-Jun expression through another positive feed-forward loop. *EGFR activating mutation.