Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells

Abstract

Fibroblast growth factor receptor-like 1 (FGFRL1) is a transmembrane receptor that interacts with heparin and FGF ligands. In contrast to the classical FGF receptors, FGFR1 to FGFR4, it does not appear to affect cell growth and proliferation. In the present study, an inducible gene expression system was utilized in combination with a xenograft tumor model to investigate the effects of FGFRL1 on cell adhesion and tumor formation. It was determined that recombinant FGFRL1 promotes the adhesion of HEK 293 Tet-On® cells in vitro. Moreover, when such cells are induced to express FGFRL1ΔC they aggregate into huge clusters. If injected into nude mice, the cells form large tumors. Notably, this tumor growth is completely inhibited when the expression of FGFRL1 is induced. The forced expression of FGFRL1 in the tumor tissue may restore contact inhibition, thereby preventing growth of the cells in nude mice. The results of the present study demonstrate that FGFRL1 acts as a tumor suppressor similar to numerous other cell adhesion proteins. It is therefore likely that FGFRL1 functions as a regular cell-cell adhesion protein.

miR‑210 promotes human osteosarcoma cell migration and invasion by targeting FGFRL1

“…FGFRL1 is newly described and usually expressed in adult pancreas and embryonic bone ( 34 ). A study has demonstrated that FGFRL1 overexpression in HEK 293 Tet-On cells suppresses the development of tumor in nude mice ( 35 ). For another example, FGFRL1 can't enhance cell proliferation but induce cell adhesion ( 36 ).…”

New developments in the biology of fibroblast growth factors

“…No function has been attributed to the short intracellular histidine‐rich domain of FGFRL1, as mice in which this domain is replaced with green fluorescent protein (GFP) are phenotypically normal (Bluteau et al, 2014). The critical molecular functions of FGFRL1 are not well defined; however, proposed functions include binding FGF ligands as a decoy receptor, dimerization‐induced inhibition of tyrosine kinase FGFRs, modulation of receptor turnover or signaling, or FGF‐independent regulation of cell adhesion or cell fusion (Trueb, 2011; Zhuang et al, 2016). Other studies show that FGFRL1 may activate FGF signaling pathways and promote resistance to chemotherapy in small cell lung cancer cell lines (R. Chen, Li, Zheng, et al, 2020).…”

FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention

“…The biological function of FGFR5 is unclear. A recent study suggested that it functions as a cell-cell adhesion protein, acting as a tumor suppressor gene [10].…”