Molecular mechanism characterizing colorectal cancer

Research published in the journal Journal of Experimental and Clinical Cancer Researchshows that blocking the binding between CDH17/DSC1 proteins will provide a new strategy to combat metastatic dissemination in patients with metastatic colorectal cancer.

“Taken together, these results shed new light on multiple functions of cadherin protein 17 (CDH17) in colorectal cancer metastasis and identification of new therapeutic targets“, says the researcher Ignacio Casalfrom the Margarita Salas Biological Research Center (CSIC), who led the study.

The combination of CDH17 and desmocholine 1 (DSC1) proteins plays a key role in the metastasis (or spread of tumor cells to form tumors in other organs) of colorectal cancer. “Our studies showed that CDH17, a key player in promoting colorectal cancer metastasis, can bind to DSC1, a desmosomal protein regulate migration and invasion in colorectal cancer tumors mesenchymal or poorly differentiated,” says Casal.

DSC1 protein silencing

“Proteomic analysis and animal models in natural conditions allowed us to demonstrate that the DSC1/CDH17 complex causes the recruitment of p120-catenin through the cytoplasmic domain of DSC1,” explains the researcher. “Immunohistochemical analyzes have demonstrated that DSC1 is expressed at high levels at the invasive tumor front in colorectal cancer biopsies, suggesting that DSC1 stabilizes the formation of groups of migrating cells and possibly circulating tumor cells (CTCs),” he adds.

The researchers observed that the suppression of the DSC1 protein in metastatic mesenchymal colorectal cancer cells reaches greater survival rate of treated mice, by inhibiting localization in the liver during metastasis.

Moreover, the authors demonstrate that the NLV sequence in CDH17 is a possible binding motif used by CDH17 to bind DSC1. The synthetic NLV peptide blocked the binding of CDH17 to DSC1, inhibiting cancer cell migration, invasion and metastasis.

These results open the door to the development of new therapeutic strategies for the treatment of metastatic colorectal cancer.

Scientific link:

Ruben A. Bartolome, Laura Pintado-Berninches, Angela Martín-Regalado, Javier Robles, Tania Calvo-López, Marina Ortega-Sapero, Celia Llorente-Sáez, Issam Bukic, Maria Jesús Fernández-Aceñero, and J. Ignacio Casal. The complex of cadherin 17 with desmocollin 1 and p120-catenin regulates colorectal cancer migration and invasion according to cellular phenotype.. (2024) J Exp Clin Cancer Res. https://doi.org/10.1186/s13046-024-02956-6

Fountain: CSIC