00085472can123565-sup-movie_4_avi_file_-_879k.avi (879.83 kB)

Movie 4 from ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

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posted on 2023-03-30, 22:08 authored by Angie Molina, Lauriane Velot, Lydia Ghouinem, Mohamed Abdelkarim, Benjamin Pierre Bouchet, Anny-Claude Luissint, Imène Bouhlel, Marina Morel, Elène Sapharikas, Anne Di Tommaso, Stéphane Honoré, Diane Braguer, Nadège Gruel, Anne Vincent-Salomon, Olivier Delattre, Brigitte Sigal-Zafrani, Fabrice André, Benoit Terris, Anna Akhmanova, Mélanie Di Benedetto, Clara Nahmias, Sylvie Rodrigues-Ferreira

Movie 4 AVI file - 879K, Time-lapse videomicroscopy of wound healing assay using GFP-ATIP3-transiently transfected D3H2LN cells

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ARTICLE ABSTRACT

Metastasis, a fatal complication of breast cancer, does not fully benefit from available therapies. In this study, we investigated whether ATIP3, the major product of 8p22 MTUS1 gene, may be a novel biomarker and therapeutic target for metastatic breast tumors. We show that ATIP3 is a prognostic marker for overall survival among patients with breast cancer. Notably, among metastatic tumors, low ATIP3 levels associate with decreased survival of the patients. By using a well-defined experimental mouse model of cancer metastasis, we show that ATIP3 expression delays the time-course of metastatic progression and limits the number and size of metastases in vivo. In functional studies, ATIP3 silencing increases breast cancer cell migration, whereas ATIP3 expression significantly reduces cell motility and directionality. We report here that ATIP3 is a potent microtubule-stabilizing protein whose depletion increases microtubule dynamics. Our data support the notion that by decreasing microtubule dynamics, ATIP3 controls the ability of microtubule tips to reach the cell cortex during migration, a mechanism that may account for reduced cancer cell motility and metastasis. Of interest, we identify a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration. Our study is a major step toward the development of new personalized treatments against metastatic breast tumors that have lost ATIP3 expression. Cancer Res; 73(9); 2905–15. ©2013 AACR.