Transcription aspect family, by facilitating its turnover through proteasomes [95]. Cathepsin S (CatS) contributes to cancer progression by mediating autophagy. In human glioblastoma cells, CatS inhibition induces autophagy and an intrinsic pathway of apoptosis as a consequence of the production of reactive oxygen species [968] and subsequent suppression of PI3K/ AKT/mTOR signaling and activation of JNK signaling [97]. Additionally, CatS inhibition could also induce autophagy by activating the EGF receptor-related ERK/ MAPK signaling pathway [99]. Cathepsin K (CatK) is primarily implicated in bone matrix resorption; however, it modulates cancer signaling by regulating the TLR and Notch pathways [100,101]. In addition, CatK may possibly regulate cytokines that are relevant for cellular crosstalk [10204]. Furthermore, CatC promotes proliferation and metastasis in hepatocellular carcinoma by interacting using the tumor necrosis element a (TNF-a)/p38 MAPK signaling pathway [105]. CatX also interferes with key signaling pathways, facilitating IGF signaling and affecting downstream signaling via focal adhesion kinase (FAK) [106]. CatX is also involved inside the MAPK/ERK and PI3K/Akt signalingpathways [68]. Furthermore, many research demonstrated that CatX importantly contributes to tumor cell signal transduction because of its interaction with integrin receptors [107]. By way of integrin-mediated pathways, CatX Serine/Threonine Kinase 40 Proteins Purity & Documentation interacts using the FAK/Src signaling pathway and dysregulates cell migration [108]. Legumain promotes tumor progression via the PI3K/ Akt signaling pathway [16] and cleaves tumor suppressor p53 in glioblastoma cells [109]. Additionally, inhibition on the p53 pathway and activation of the MYC pathway by legumain secreted from glioblastoma cells result in the malignant transformation of normal astrocytes, which enhances the invasive capacity of glioblastoma cells [110]. Tumor-derived legumain interacts with endothelial integrin avb3 via its Arg-Gly-Asp (RGD) motif and indirectly downregulates the expression of zonula occludens 1 by means of the STAT3 signaling pathway, which can promote tumor metastasis by rising the permeability of endothelial barriers [111,112]. In addition, in TrkC Proteins Storage & Stability ovarian carcinoma cells, legumain interacts with integrin a5b1 and types complexes that happen to be secreted. These complexes are internalized by peritoneal mesothelial cells, in which they promote proliferation and migration by way of the FAK/Akt/ ERK signaling pathways and contribute to EMT [113]. Each the proform and mature types of CatD boost cancer progression via both proteolytically dependent and independent manners [114]. ProCatD acts as a protein ligand and stimulates the proliferation of breast cancer cells by means of an autocrine mechanism. It interacts together with the IGF-II receptor and can bind for the M6P/IGF-II receptor around the surface of breast cancer cells [115]. Both CatD and pro-CatD also market cancer proliferation and migration by inducing phosphorylation of ERK and PI3K/Akt via a nonproteolytic mechanism [116,117]. In addition, it induces the outgrowth of fibroblasts by binding towards the receptor on the low-density lipoprotein receptor-related protein 1, hence inhibiting intermembrane proteolysis that is regulated by this protein [118]. CatG interacts with oncogenic proteins from the TGF-b pathway. It promotes TGF-b signaling at the tumor one particular interface by proteolytic activation of matrix metallopeptidase 9 (MMP9), thus promoting tumor development and enhancing osteoclast activation and subsequent bone r.