TY - JOUR T1 - Involvement of I-BAR protein IRSp53 in tumor cell growth via extracellular microvesicle secretion JF - bioRxiv DO - 10.1101/2020.04.20.050492 SP - 2020.04.20.050492 AU - Hooi Ting Hu AU - Naoto Sasakura AU - Daisuke Matsubara AU - Naoko Furusawa AU - Masahiro Mukai AU - Narufumi Kitamura AU - Takeshi Obayashi AU - Tamako Nishimura AU - Kayoko Oono-Yakura AU - Yosuke Funato AU - Yasunobu Okamura AU - Kento Tarao AU - Yasushi Nakano AU - Yoshinori Murakami AU - Kengo Kinoshita AU - Chiaki Takahashi AU - Hiroaki Miki AU - Kohsuke Gonda AU - Giorgio Scita AU - Kyoko Hanawa-Suetsugu AU - Shiro Suetsugu Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/20/2020.04.20.050492.abstract N2 - Cellular protrusions mediated by the membrane-deforming I-BAR domain protein IRSp53 are involved in cell migration, including metastasis. However, the role of IRSp53 in cell proliferation remains unclear. Here, we examined the role of IRSp53 in cell proliferation and found that it acts through secretion. Coculture of gingiva squamous carcinoma Ca9-22 cells and their IRSp53-knockout cells restored proliferation to parental Ca9-22 cell levels, suggesting possible secretion dependent on IRSp53. Notably, the amounts of microvesicle fraction proteins that were secreted into the culture medium were reduced in the IRSp53-knockout cells. The IRSp53-knockout cells exhibited decreased phosphorylation of mitogen-activated protein kinase, suggesting the decrease in the proliferation signals. The phosphorylation was restored by the addition of the microvesicles. In mice xenograft Ca9-22 cells, IRSp53-containing particles were secreted around the xenograft, indicating that IRSp53-dependent secretion occurs in vivo. In a tumor mice model, IRSp53 deficiency elongated lifespan. In some human cancers, the higher levels of IRSp53 mRNA expression was found to be correlated with shorter survival years. Therefore, IRSp53 is involved in tumor progression and secretion for cellular proliferation. ER -