Figure 2.

Effects of stress on cancer initiation, progression, metastasis and underlying mechanisms. The schematic diagram presents the effects of stress on the biological behaviours of tumours. Glucocorticoids and catecholamines produced by the activated neuroendocrine stress system are involved in tumour regulation by binding to their respective receptors. Stress may promote tumorigenesis through genomic instability, DNA damage, the reactivation of latent oncogenic infections, the upregulation of oncogenes, the acquisition of stem cell-like characteristics and eventually, malignant transformation. Stress can facilitate tumour progression through various mechanisms, including alterations in the tumour microenvironment through the stimulation of MMPs, ECM remodelling, neo-angiogenesis and neurogenesis. Stress can promote tumour metastasis by establishing a premetastatic microenvironment and premetastatic niches, and by remodelling the lymphatic vasculature. Distress can induce pro-inflammatory conditions, as well as immune suppression, by reducing the infiltration and function of effector immune cells, such as TH and NK cells, and by promoting the infiltration and function of suppressive cells, including TH2 cells, M2 Mφ (macrophages), and TAMs. C-Myc, cellular myelocytomatosis oncogene; COX2, cyclooxygenase 2; Src, proto-oncogene tyrosine-protein kinase Src; IL, interleukin; VEGF, vascular endothelial growth factor; TSP1, thrombospondin 1 (anti-angiogenic factor); MMPs, matrix metalloproteinases; ECM, extracellular matrix; TH1, T-helper 1 cells; TH2, TH1, T-helper 2 cells; NK, natural killer; TAMs, tumour-associated macrophages. Parts of this image were derived from the free medical site http://smart.servier.com/ (accessed on July 15, 2023) by Servier, licenced under a Creative Commons Attribution 3.0 Unported Licence.