Abstract 2938: Transmembrane chloride intracellular channel 1 (tmCLIC1) correlates with metastatic potential of colorectal cancer cells

Abstract

Abstract Colorectal cancer (CRC) is the third most common and lethal tumor worldwide. Although CRC can be efficiently eradicated when diagnosed in the early stage, no effective therapies are currently available for advanced metastatic disease. Therefore, targeting metastasis represents a critical challenge for the successful treatment of CRC. To achieve this purpose, our laboratory has found a promising candidate inthe transmembrane localized Chloride Intracellular Channel 1 (tmCLIC1) protein. Growing scientific evidence have suggested an involvement of tmCLIC1 in different human malignancies, including CRC, with an unknown mechanism. CLIC1 is a metamorphic protein able to shuttle between a soluble cytoplasmic and a membrane integrated form, the latter characterized by ionic channel function. In normal cells, it is mostly cytoplasmic and cooperates to the maintenance of several physiological processes. Otherwise, in cancer cells CLIC1 undergoes to chronic membrane insertion, where contributes to the abnormal cellular hyperproliferative rate.In the present investigation, using CRC human cell lines at different stage of tumor development, we demonstrate that tmCLIC1 functional expression correlates with CRC cells increasing aggressiveness, while it is almost absent in normal colon cells. We also show that CLIC1 enrichment in plasma membrane is involved in promotion of CRC metastasis. CLIC1 inhibition using different pharmacological treatments led to drastic reduction of cell proliferation, migration and invasiveness.tmCLIC1 function permits to discriminate between normal and malignant cells and its downregulation is able to arrest metastatic cells. This is not the case of other upregulated proteins not only involved in tumorigenesis but also in physiological cell functions. Since metastasis are considered the leading cause of treatment failure and tumor relapse, CLIC1 inhibition coupled to conventional therapies can represent a novel strategy to successfully treat CRC with reduced side effects. (This work is supported by a GRANT from AIRC to MM) Citation Format: Valentina Carlini, Francesca Cianci, Ivan Verduci, Michele Mazzanti. Transmembrane chloride intracellular channel 1 (tmCLIC1) correlates with metastatic potential of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2938.