IMIM: Key piece identified for slowing a colorectal cancer subtype

IMIM: Key piece identified for slowing a colorectal cancer subtype

News from IMIM

Inhibiting the Jagged 1 protein in mice prevents the proliferation and growth of colon and rectal tumours. What is more, this approach to the disease permits the removal of existing tumours. This is the conclusion of a study led by the Molecular Mechanisms of Cancer and Stem Cells research group from the Hospital del Mar Medical Research Institute (IMIM), directed by Dr Lluís Espinosa, who is also a member of CIBERONC (the Network Centre for Biomedical Research into Cancer), in collaboration with the Pathological Anatomy and Medical Oncology Units at Hospital del Mar, and the IDIBELL-Catalan Oncology Institute. The work has been published in Nature Communications.

In this study, the researchers discovered that the intestinal tumours of mice lack a protein known as Fringe, implying that Jagged 1 is essential for activating Notch. "The fact that Fringe is present in the normal cells of the small intestine represents a significant therapeutic opportunity for treating patients with colorectal cancer", says Dr Espinosa, since by inhibiting Jagged 1 you can halt tumour growth without affecting the function of normal tissue.

In fact, researchers have been able to see how, in the case of healthy mice, the colon and rectum do not need Jagged 1, since in the presence of the Fringe protein there are other mechanisms for activating Notch. This need to have Jagged 1 in order to activate Notch in the absence of Fringe was observed in 239 of the cases of human tumours that were analysed. Therefore, inhibiting this protein could enable doctors to combat the disease without affecting the functioning of the body. Dr Espinosa explains that "we implanted human tumours with Jagged 1, without Fringe, into mice and then we treated them with antibodies. Post-treatment, the tumours were very small and had necrosed." In the study, the tumours had shrunk after 10 weeks of treatment.

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Reference article:
López-Arribillaga, E, Rodilla V, Colomer C, Vert A, Shelton A, Cheng JH, Yan B, Gonzalez-Perez A, Junttila MR, Iglesias M, Torres F, Albanell J, Villanueva A, Bigas A, Siebel CW, Espinosa LL. Manic Fringe deficiency imposes Jagged1 addiction to intestinal tumor cells. Nature Communications. DOI: 10.1038/s41467-018-05385-0 NCOMMS-16-29845.