The cancer-associated cell migration protein TSPAN1 is under control of androgens and its upregulation increases prostate cancer cell migration

Abstract

Cell migration drives cell invasion and metastatic progression in prostate cancer and is a major cause of mortality and morbidity. However the mechanisms driving cell migration in prostate cancer patients are not fully understood. We previously identified the cancer-associated cell migration protein Tetraspanin 1 (TSPAN1) as a clinically relevant androgen regulated target in prostate cancer. Here we find that TSPAN1 is acutely induced by androgens, and is significantly upregulated in prostate cancer relative to both normal prostate tissue and benign prostate hyperplasia (BPH). We also show for the first time, that TSPAN1 expression in prostate cancer cells controls the expression of key proteins involved in cell migration. Stable upregulation of TSPAN1 in both DU145 and PC3 cells significantly increased cell migration and induced the expression of the mesenchymal markers SLUG and ARF6. Our data suggest TSPAN1 is an androgen-driven contributor to cell survival and motility in prostate cancer.Cancer, in its most aggressive form, is not only a disease of uncontrolled cell growth, but also a disease of inappropriate cell migration. Activating invasion and metastasis is a hallmark of cancer progression 1, 2 and is the leading cause of mortality among cancer patients 3 . Metastasis involves cancer cells detaching from the primary tumour, and travelling as circulating tumour cells through the bloodstream or lymphatic system to other parts of the body. Prostate cancer is the most common male cancer in Europe, with around 50,000 new cases in the UK each year 4 . At initial diagnosis 37-43% of men have late stage disease and 17-34% of prostate cancer patients have metastasis (http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ prostate-cancer/incidence#ref-8). The development of prostate cancer is initially driven by androgen steroid hormones via the androgen receptor (AR) transcription factor. The first line treatment for prostate cancer that is no longer organ confined is androgen deprivation therapy (ADT). However, after 2-3 years many patients develop

TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance

“…Thus, TSPAN1 expression was detected in~45% (IHC) of laryngeal and pharyngeal tumors, a similar percentage to the upregulation of TSPAN1 detected at mRNA level (8 out of 16 patients) and also by Western blot (eight out of 12 patients). In good agreement, the overexpression of TSPAN1 in human cancer vs. adjacent non-cancerous tissue has been widely documented in cholangiocarcinoma [31,47,48], skin squamous cell carcinoma [36,49], esophageal carcinoma [34], ovarian carcinomas [50], prostate cancer [26], pancreatic cancer [35,37] and gastric carcinoma [51,52]. Moreover, TSPAN1 expression has been associated with HPV infection in cervical carcinomas, and considered an important diagnostic and prognostic marker, as strong TSPAN1 expression was found in a subset of high-grade cervical cancers and in most of the undifferentiated squamous cell carcinomas [53][54][55].…”

“…TSPAN1 protein expression in tumors exhibited cytoplasmic and nuclear patterns that were separately scored, whereas TSPAN1 expression was negligible in matched adjacent normal epithelia and stromal cells ( Figure 6B). Although the cytoplasmic expression of TSPAN1 has been reported, we have not found previous works describing nuclear expression [26,31,33]. Forty-eight (45.2%) out of 106 patients showed cytoplasmic TSPAN1, and 34 of them showed concomitant cytoplasmic and nuclear staining (32.1% of total) ( Figure 6C).…”

“…Finally, 36 proteins were commonly and differentially expressed in CCL-138-R and CSCs compared to parental CCL-138 cells; 12 proteins were upregulated and 24 proteins downregulated ( Figure 1A, Table S6). One of the most upregulated protein, a member of the tetraspanin family, named TSPAN1, was primarily selected for its potential clinical interest in various cancer models [26,27]. In order to explore the putative relevance of TSPAN1 in HNSCC, TSPAN1 levels were compared in the following HNSCC cell lines: CCL-138, JHU029, HTB-43 and SSC-25.…”

HNF1B expression regulates ECI2 gene expression, potentially serving a role in prostate cancer progression

“…Cancer of the prostate is the most common type of cancer in the USA and was the second leading cause of cancer-associated mortality in 2016 (1). Uncontrolled growth associated with cellular migration and metastasis is the leading cause of cancer-associated mortality (2), with 17–34% of patients exhibiting metastatic disease at the time of initial diagnosis (3). Late-stage diagnosis remains an important problem, accounting for 37–43% of all cases, and is a significant risk factor for disease-associated mortality.…”

Tetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta‐catenin pathway in human pulmonary fibrosis

“…27 However, it is observed opposite effect that TSPAN1 control cell migration in prostate cancer. 21,28 These reports confirmed that TSPAN1 participate cell migration and invasion in some human cancer, meantime, indicating TSPAN1 may be involved in complex signalling pathway and dependent-tissue specificity. Epithelial-to-mesenchymal transition was considered to be a mechanism of epithelial cells' transformation in IPF.…”