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Review
. 2025 Apr 6;16(4):437.
doi: 10.3390/genes16040437.

RON Receptor Signaling and the Tumor Microenvironment

Emily Wachter  1 , Levi H Fox  1 , Zhixin Lu  1 , Angelle D Jones  1 , Nicholas D Casto  1 , Susan E Waltz  1   2
Affiliations
Review

RON Receptor Signaling and the Tumor Microenvironment

Emily Wachter et al. Genes (Basel). .

Abstract

The immune microenvironment plays a critical role in tumor growth and development. Immune activation within the tumor microenvironment is dynamic and can be modulated by tumor intrinsic and extrinsic signaling. The RON receptor tyrosine kinase is canonically associated with growth signaling and wound healing, and this receptor is frequently overexpressed in a variety of cancers. Epithelial cells, macrophages, dendritic cells, and fibroblasts express RON, presenting an important axis by which RON overexpressing tumors influence the tumor microenvironment. This review synthesizes the existing literature on the roles of tumor cell-intrinsic and -extrinsic RON signaling, highlighting areas of interest and gaps in knowledge that show potential for future studies.

Keywords: HGFL; RON; RTK; cancer; immune microenvironment; interferons; macrophages; metastasis; mouse models; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Crosstalk between RON-expressing tumor cells and macrophages enables a pro-tumor, immunosuppressive microenvironment. RON expression in cancer cells models the tumor microenvironment through regulation of immune populations as well as promotion of stromal remodeling and angiogenesis. RON expression in macrophages is critical in supporting tumor cell-intrinsic phenotypes and in supporting pro-tumor immune regulation. The crosstalk between tumor cells and macrophages enabled by RON promotes enhanced cancer cell growth, metastasis, and therapeutic resistance.
See this image and copyright information in PMC

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