Cathepsin B: A sellsword of cancer progression

Abstract

Clinical, biochemical and molecular biology studies have identified lysosome-encapsulated cellular proteases as critical risk factors for cancer progression. Cathepsins represent a group of such proteases aimed at maintenance of cellular homeostasis. Nevertheless, recent reports suggest that Cathepsin B executes other cellular programs such as controlling tumor growth, migration, invasion, angiogenesis, and metastases development. In fact, elevated levels of Cathepsins are found under different pathological conditions including inflammation, infection, neurodegenerative disease, and cancer. Furthermore, the discovery of Cathepsin B secretion and function as an extracellular matrix protein has broadened our appreciation for the impact of Cathepsin B on cancer progression. Underneath a façade of an intracellular protease with limited therapeutic potential hides a central role of cathepsins in extracellular functions. Moreover, this role is incredibly diverse from one condition to the next -from driving caspase-dependent apoptosis to facilitating tumor neovascularization and metastasis. Here we discuss the role of Cathepsin B in the oncogenic process and perspective the use of Cathepsin B for diagnostic and therapeutic applications.

Proteomic and Transcriptomic Profiling Identifies Early Developmentally Regulated Proteins in Dictyostelium Discoideum

“…DDB0349243 is an ortholog of human Cathepsin B, which is believed to participate in intracellular degradation and turnover of proteins, including the matrix extracellular phosphoglycoprotein MEPE [143]. It has also been implicated in tumor invasion and metastasis [144]. Adenylylsulfate kinase has a human ortholog named PAPSS2, which is a bifunctional enzyme with both ATP sulfurylase and APS kinase activity, that mediates two steps in the sulfate activation pathway.…”

Cathepsin B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes

“…These results support the hypothesis that CTSB is associated with pancreatic cancer progression. It has been reported that CTSB contributes generally to tumor growth, migration, invasion and angiogenesis (38). Notably, the observation of both expressions of CTSB and its inhibitors in tumor tissues and tumor-infiltrating immune cells had suggested that those may be involved in pancreatic ductal adenocarcinoma-related inflammation (41).…”

“…The function of CTSB is dynamic and poorly understood; however, it is hypothesized that CTSB encoding lysosomal proteinase plays a role in not only in normal physiological conditions but also in pathological conditions, such as inflammation, infection and neurodegenerative disease, and the malignant progression of several cancer types including gastric, colorectal, breast and pancreatic cancers ( 34 – 38 ). It remains unclear whether CTSB is expressed in tumor cells, tumor-related cells, or both, and whether CTSB expression affects or is affected by interactions with cellular and/or non-cellular microenvironments ( 21 ).…”

Cepharanthine as a Potential Novel Tumor-Regional Therapy in Treating Cutaneous Melanoma: Altering the Expression of Cathepsin B, Tumor Suppressor Genes and Autophagy-Related Proteins

“…Cathepsin B, a member of the cysteine protease family, hydrolyzes various extracellular matrix components and disrupts their mucosal barrier in pathological conditions. In recent years, cathepsin B has been considered a sword in the evolution of cancer (Mijanović et al, 2019). Aberrant regulation of cathepsin B expression correlates with the invasive and metastatic phenotype of cancer (Tomita et al, 1967).…”

“…Cepharanthine (CEP, Figure 1), a natural alkaloid extracted from the genus Cephalophyllum and has been reported to have cathepsin B inhibitory function and to induce autophagy-related cell death in several cancer cells (Mijanović et al, 2019). CEP has been explored in many diseases such as cancer, alopecia areata, snakebite, and malaria (Saito et al, 1989).…”