Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

Abstract

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial (“mesenchymal”) transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies.

Mapping Cellular Interactions from Spatially Resolved Transcriptomics Data

“…The “EMT score” of a tumor cell is defined to be the mean expression of the EMT marker genes from Gorgola et al ( 84 ): FN1, TWIST1, SNAI1, SNAI2, ZEB1, TGFB1, TGFB2, and CTNNB1 , which represents the activity level of EMT in that tumor cell. We performed additional analyses to validate that this EMT score is valid in our scRNA-seq datasets ( Sup.…”

“…The "EMT score" of a tumor cell is defined to be the mean expression of the EMT marker genes from Gorgola et al (82): FN1, TWIST1, SNAI1, SNAI2, ZEB1, TGFB1, TGFB2, and CTNNB1, which represents the activity level of EMT in that tumor cell.…”

Promoter hypermethylation as a novel regulator of ANO1 expression and function in prostate cancer bone metastasis

“…Prostate cancer constitutes a significant health burden, being the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among men in the United States 11 . Prostate cancer can be diagnosed as a localized or advanced disease, with several treatment options including surgery, radiation therapy, hormonal therapy, chemotherapy, immunotherapy, and combinations of these therapies 12 , 13 .…”

“…However, the development of effective therapies for this advanced prostate cancer still remains a major clinical challenge. The process of tumor development and metastasis is multifaceted, and involves misregulation of both proto-oncogenes and tumor suppressor genes 11 , 15 , 16 . Also, functional inactivation of growth-inhibitory factors can lead to uncontrolled cell cycling and aberrant cell growth in those pathogenic processes 11 , 15 .…”

“…The process of tumor development and metastasis is multifaceted, and involves misregulation of both proto-oncogenes and tumor suppressor genes 11 , 15 , 16 . Also, functional inactivation of growth-inhibitory factors can lead to uncontrolled cell cycling and aberrant cell growth in those pathogenic processes 11 , 15 . Accordingly, the identification of specific molecular alterations that underlie the pathogenesis of prostate cancer metastasis may hold promise for predicting the clinical course and aggressiveness of newly diagnosed cases.…”