RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis

Chi3l1 is induced by a variety of cancers where it portends a poor prognosis and plays a key role in the generation of metastasis. However, the mechanisms that Chi3l1 uses to mediate these responses and the pathways that control Chi3l1-induced tumor responses are poorly understood. We characterized the mechanisms that Chi3l1 uses to foster tumor progression and the ability of the RIG-like helicase (RLH) innate immune response to control Chi3l1 elaboration and pulmonary metastasis. Here we demonstrate that RLH activation inhibits tumor induction of Chi3l1 and the expression of receptor IL-13Rα2 and pulmonary metastasis while restoring NK cell accumulation and activation, augmenting the expression of IFN-α/β, chemerin and its receptor ChemR23, p-cofilin, LIMK2 and PTEN and inhibiting BRAF and NLRX1 in a MAVS-dependent manner. These studies demonstrate that Chi3l1 is a multifaceted immune stimulator of tumor progression and metastasis whose elaboration and tissue effects are abrogated by RLH innate immune responses.