NK cell expansion requires the RNA-binding protein HuR to control solid tumors but not tumor metastases

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B979
Abstract ID: 7888

Presenting Author:
Sytse J Piersma , Instructor at Washington Univ. Sch. of Med., St. Louis, Siteman Cancer Ctr., Barnes-Jewish Hosp. and Washington Univ. Sch. of Med., St. Louis

Abstract:

Natural killer (NK) cells are capable of controlling tumors through direct lysis and cytokine production. NK cells also expand and accumulate in affected tissues, but the role of NK cell expansion in tumor control is not well understood. Here, we show that post-transcriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without overtly affecting NK cell effector functions. Mice that lacked HuR specifically in NK cells were deficient in controlling solid tumors but were fully capable of eliminating tumor metastases in 2 independent tumor models. Mechanistically, HuR-deficient NK cells displayed defects in the expression and splicing of cell cycle-associated genes, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex that is involved in chromosome separation during cell division. These results show that post-transcriptional regulation by HuR specifically affects NK cell expansion which is required for controlling multiple solid tumor models but is dispensable in corresponding tumor metastasis models. Thus, our results underline different requirements for NK cells to control primary tumors versus metastasizing tumors.