Clinical Significance of Hepsin and Underlying Signaling Pathways in Prostate Cancer

Abstract

The hepsin gene encodes a type II transmembrane serine protease. Previous studies have shown the overexpression of hepsin in prostate cancer, and the dysregulation of hepsin promotes cancer cell proliferation, migration, and metastasis in vitro and in vivo. The review incorporated with our work showed that hepsin expression levels were specifically increased in prostate cancer, and higher expression in metastatic tumors than in primary tumors was also observed. Moreover, increased expression was associated with poor outcomes for patients with prostate cancer. Using in silico protein–protein interaction prediction, mechanistic analysis showed that hepsin interacted with eight other oncogenic proteins, whose expression was significantly correlated with hepsin expression in prostate cancer. The oncogenic functions of hepsin are mainly linked to proteolytic activities that disrupt epithelial integrity and regulatorily interact with other genes to influence cell-proliferation, EMT/metastasis, inflammatory, and tyrosine-kinase-signaling pathways. Moreover, genomic amplifications of hepsin, not deletions or other alterations, were significantly associated with prostate cancer metastasis. Targeting hepsin using a specific inhibitor or antibodies significantly attenuates its oncogenic behaviors. Therefore, hepsin could be a novel biomarker and therapeutic target for prostate cancer.

Comparative Assessment of the Antioxidant and Anticancer Activities of Plicosepalus acacia and Plicosepalus curviflorus: Metabolomic Profiling and In Silico Studies

“…Among women, ovarian and breast carcinomas are the most prevalent invasive and lethal malignancies [ 8 , 9 , 10 , 11 ]. Meanwhile, prostatic neoplasms are the most frequently diagnosed cancers in men, and are considered the third-leading cause of cancer-related deaths in the USA [ 7 , 12 ]. In past decades, immense advances in cancer research were achieved, especially in the provision of targeted prevention and treatments, which improved the quality of life and survival time remarkably.…”

“…In past decades, immense advances in cancer research were achieved, especially in the provision of targeted prevention and treatments, which improved the quality of life and survival time remarkably. Nevertheless, cancer treatment remains a tremendous challenge due to its severe adverse effects, chemotherapy resistance or tumor progression and metastasis, and therefore worse prognoses [ 1 , 2 , 9 , 12 ]. Thus, there is an increased demand for new anticancer candidates to face these health concerns and reduce the cancer burden worldwide [ 5 , 6 ].…”

Lipid-Based Nanotechnology: Liposome

“…This RIPL peptide was conjugated with a liposome, creating RIPL peptide-conjugated liposomes [ 132 , 133 ]. The IPL component in this strategy targets hepsin, a protein overexpressed in cancer cells, exhibiting high affinity and selectivity to IPL peptides [ 134 ]. Consequently, this approach significantly enhances cellular uptake and strengthens selective binding with the RIPL–liposome conjugates [ 135 ].…”

Genome-Wide Identification of Trachinotus ovatus Antimicrobial Peptides and Their Immune Response against Two Pathogen Challenges

“…Although the expression of ubtd1 presented slight fluctuations with the intensification of pathogen stimulation, no strong upregulation of expression was observed. This suggests that when pathogen stimulation occurs, the hpn gene in the liver may respond first, regulating interactions with other genes to affect cell proliferation, EMT/metastasis, inflammation, and tyrosine kinase signaling pathways through the hydrolysis of proteases [76]. Low ubtd1 expression induces RhoA activation, increases cell traction forces, and activates YAP signaling via ROCK2 fostering cancer cell aggressiveness [50,77].…”