ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line

Abstract

Interferon gamma (IFN-ɣ) is a pleiotropic cytokine which plays dual contrasting roles in cancer. Although IFN-ɣ has been clinically used to treat various malignancies, it was recently shown to have protumorigenic activities. Reactive oxygen species (ROS) are overproduced in cancer cells, mainly due to NADPH oxidase activity, which results into several changes in signaling pathways. In this study, we examined IFN-ɣ effect on the phosphorylation levels of key signaling proteins, through ROS production, in the human breast cancer cell line MCF-7. After treatment by IFN-ɣ, results showed a significant increase in the phosphorylation of STAT1, Src, raf, AKT, ERK1/2 and p38 signaling molecules, in a time specific manner. Src and Raf were found to be involved in early stages of IFN-ɣ signaling since their phosphorylation increased very rapidly. Selective inhibition of Src-family kinases resulted in an immediate significant decrease in the phosphorylation status of Raf and ERK1/2, but not p38 and AKT. On the other hand, IFN-ɣ resulted in ROS generation, through H 2 O 2 production, whereas pre-treatment with the ROS inhibitor NAC caused ROS inhibition and a significant decrease in the phosphorylation levels of AKT, ERK1/2, p38 and STAT1. Moreover, pretreatment with a selective NOX1 inhibitor resulted in a significant decrease of AKT phosphorylation.Finally, no direct relationship was found between ROS production and calcium mobilization. In summary, IFN-ɣ signaling in MCF-7 cell line is ROS-dependent and follows the Src/ Raf/ERK pathway whereas its signaling through the AKT pathway is highly dependent on NOX1.

EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer

“…These data suggest that c-RAF signaling is a dominant factor in the IFNγ/TNFα-mediated induction of chemokine expression in the HNC cell lines. Our observations are sustained by other studies showing that activation of the IFNγR and the TNFR can result in the activation of RAF [ 26 , 27 ].…”

Functionalization of Ti substrate with pH‐responsive naringin‐ZnO nanoparticles for the reconstruction of large bony after osteosarcoma resection

“…On one hand, the accumulation of ROS in bacteria and osteosarcoma result in damage of nucleic, amino acids, and membrane lipids (Sultana et al, 2015; Van Acker & Coenye, 2017; Zhao & Drlica, 2014). On the other hand, the increase of ROS can induce osteosarcoma cell apoptosis by activating ROS/ERK signaling pathway (Wang, Hou, et al, 2017; Zibara et al, 2017). The anti‐bacterial and anti‐osteosarcoma abilities can be increased obviously when ZnO nanoparticles are decorated with NG.…”

“…As a critical factor affecting several cancer hallmarks, ROS is also involved in the acquisition of self‐sufficiency in proliferation signals by a ligand‐independent receptor tyrosine kinase transactivation as well as the loss of contact inhibition and anchorage‐dependence cell growth (Godet et al, 2019; Ishikawa et al, 2008; Poillet‐Perez, Despouy, Delage‐Mourroux, & Boyer‐Guittaut, 2015; Wang, Hou, Su, Zhao, & Shi, 2017). Moreover, ROS can affect many signaling pathways, including mitogen‐activated protein kinases signaling pathways (MAPK) (Avisetti, Babu, & Kalivendi, 2014; Shen & Liu, 2006; Zibara et al, 2017). As a member of the MAPK family, extracellular signal‐regulated kinase (ERK) in apoptosis, autophagy, and many other cells play an important role in biological events (Martinez‐Lopez, Athonvarangkul, Mishall, Sahu, & Singh, 2013; Sun et al, 2015).…”

Obesity‐induced MBD2_v2 expression promotes tumor‐initiating triple‐negative breast cancer stem cells

“…Circulating IFNc is produced by adipocytes in obese individuals, and IFNc levels are elevated by DIO in B6.Rag1À/À mice Wentworth et al, 2017). Activation of breast cancer cell IFNc receptors increases ROS levels, specifically hydrogen peroxide (Zibara et al, 2017). Also in obese breast cancer patients, increased macrophage infiltration of breast adipose tissue yields additional paracrine-acting pro-inflammatory cytokines (Vaysse et al, 2017).…”