TNF and cancer: It is well known that oxidative stress plays an obligatory role in inducing ER stress and UPR activation.29,30 For example, in response to TNF stimulation, NF-κB and JNK functioned synergistically to potentiate cellular ROS production, and lead to damaging the homeogenesis of cells.42 Oncogenes, by inducing oncogenic stress, can trigger ER stress and UPR activation during cancer genesis and development.