Metastasis frequently develops years after the removal of a primary tumor, from a minority of disseminated cancer cells that survived as latent entities through unknown mechanisms. We isolated latency competent cancer (LCC) cells from early-stage human lung and breast carcinomas and defined the mechanisms that prevent the outgrowth, support the long-term survival, and maintain the tumor-initiating potential of these cells during the latent metastasis stage. LCC cells show stem cell-like characteristics and express Sox transcription factors, which are essential for their survival in host organs under restrictive conditions and for metastatic outgrowth under permissive conditions. Through WNT inhibition, LCC cells self-impose a slow cycling state and evade immune clearance. By expressing a Sox-dependent stem-like state and actively silencing WNT signaling, LCC cells can enter quiescence and evade innate immunity to remain latent for extended periods.
Citation Format: Srinivas Malladi, Danilo G. Macalinao, Xin Jin, Lan He, Joan Massague. Metastatic latency and immune evasion mediated by autocrine WNT inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr PR06.