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GPC1 – a new target for colorectal cancer treatment

A new study has identified a protein that promotes the growth and spread of colorectal cancer, presenting a new target for treatment. Glypicans are a family of heavily glycosylated proteins found in the cell membrane. They regulate growth factor signalling and are over-expressed in several types of cancer. A new study, published in PLOS One, investigated the mechanism of action of glypican-1 (GPC1) in colorectal cancer (CRC). The study showed that this protein promotes the TGF-β signalling pathway in CRC cells and is associated with poor prognosis in patients with CRC.

Enhanced GPC1 decreases survival

The authors used data from The Cancer Genome Atlas. They then determined the predictive significance of GPC1 expression and its association with clinical and pathological features.

CRC patients with high GPC1 expression had poorer overall survival than patients with low GPC1 expression. This finding was confirmed using immunohistochemical analysis of four pairs of cancer and paracarcinoma tissues from patients with CRC. Here, the protein expression of GPC1 in tumour tissues was elevated.

These findings are consistent with previous reports, and add weight to the role of GPC1 in CRC.

Suppressing TGF-β offers a new therapeutic target

Next, the authors used bioinformatics to explore the mechanism underlying the role of GPC1 in CRC. The analysis identified GPC1-related genes, and showed that GPC1 likely regulates the TGF-β1 signalling pathway. This finding fits in with previous studies showing that the TGF-β signalling pathway is involved in the occurrence and development of CRC.

The authors then carried out in-vitro experiments in two CRC cell lines. Silencing of the GPC1 gene inhibited cell proliferation. It also inhibited migration and promoted apoptosis. Furthermore, silencing of GPC1 suppressed the levels of TGF-β1 and phosphorylated SMAD2.

The authors said, ”These findings suggest that GPC1 acts as a tumour promoter in CRC cells by activating the TGF-β signalling pathway.”

This could mean that GPC1 is e a prognostic marker and a new therapeutic target for CRC. However, the authors note that further studies using larger numbers of clinical samples are needed, as well as animal studies to determine how GPC1 affects the pathogenesis of CRC in vivo.

Written by Charlotte Harrison, Science Writer

Image Credit: Canva