Targeting cathepsin S induces tumor cell autophagy via the EGFR–ERK signaling pathway

Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non-small-cell lung cancer

“…Akhtar et al (27) reported that activation of EGFR via pathways involving ERK1/2, p38 MAPK and AKT̸FOXO promoted cardiac cell survival during ischemia-reperfusion injury. Chen et al (28) demonstrated that the surface receptor EGFR and its downstream ERK̸MAPK signaling pathway are crucial in the activation of autophagy in cathepsin S-targeted cells. Furthermore, a recent study indicated that EGFR downstream signal JNK exerts a major protective effect by increasing autophagy, leading to antagonising apoptosis and ROS generation in A431 cells (29).…”

FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells

“…For example, some agents known to induce apoptosis also activate autophagy. However, under some circumstances, autophagy acts as a protector-it protects cells from apoptosis , whereas in other situations autophagy acts as a promoter-it promotes cell apoptosis (Chen et al, 2012). The relationship between autophagy and necroptosis is also intricate.…”

Lysosomal cysteine peptidases – Molecules signaling tumor cell death and survival

“…Cathepsin S inhibition results in ERK activation and, thus, in induction of tumor cell autophagy [164].…”

“…Cathepsin Cleavage of Bid, Bcl-2 family proteins Apoptosis [140,142] Regulation of TGF-β signaling EMT [170] Cathepsin H Cleavage of Bid, Bcl-2 family proteins Apoptosis [140,142] Activation of granzymes B Granzyme-mediated apoptosis [154] Cathepsin S Cleavage of Bid, Bcl-2 family proteins Apoptosis [140,142] Regulation of PI3K/Akt/mTOR signaling Autophagy [163] Regulation of MAPK signaling Autophagy [163,164] Cathepsin K Cleavage of Bid, Bcl-2 family proteins Apoptosis [140,142] Cathepsin X Regulation of IGF-I signaling Tumor cell proliferation [125] Interaction with RPLP0 Apoptosis [144] Regulation of expression of epithelial and mesenchymal markers…”