Researchers have discovered a new mechanism that may regulate tumor cell invasion in colorectal cancer – Society

A team of researchers from the Margarita Salas Center for Biological Research (CSIC) has identified a new molecular mechanism in mice that controls the process of invasion and metastasis in colorectal cancer, which may represent a potential new therapeutic target.

The results, published in the Journal of Experimental and Clinical Cancer Research, indicate that blocking the binding between the CDH17/DSC1 proteins will provide a new strategy for preventing metastatic dissemination in patients with metastatic colorectal cancer.

“Taken together, these results shed new light on the multiple functions of the cadherin 17 (CDH17) protein in colorectal cancer metastasis and identify new therapeutic targets,” says researcher Ignacio Casal from the Margarita Salas Biological Research Center (CSIC). studying.

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, to regulate migration and invasion into mesenchymal or low-grade colorectal cancer tumors,” Casal points out.

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

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