FGF2 Antiproliferative Stimulation Induces Proteomic Dynamic Changes and High Expression of FOSB and JUNB in K‐Ras‐Driven Mouse Tumor Cells

Abstract

Fibroblast growth factor 2 (FGF2) is a well-known cell proliferation promoter; however, it can also induce cell cycle arrest. To gain insight into the molecular mechanisms of this antiproliferative effect, for the first time, the early systemic proteomic differences induced by this growth factor in a K-Ras-driven mouse tumor cell line using a quantitative proteomics approach are investigated. More than 2900 proteins are quantified, indicating that terms associated with metabolism, RNA processing, replication, and transcription are enriched among proteins differentially expressed upon FGF2 stimulation. Proteomic trend dynamics indicate that, for proteins mainly associated with DNA replication and carbohydrate metabolism, an FGF2 stimulus delays their abundance changes, whereas FGF2 stimulation accelerates other metabolic programs. Transcription regulatory network analysis indicates master regulators of FGF2 stimulation, including two critical transcription factors, FOSB and JUNB. Their expression dynamics, both in the Y1 cell line (a murine model of adenocarcinoma cells) and in two other human cell lines (SK-N-MC and UM-UC-3) also susceptible to FGF2 antiproliferative effects, are investigated. Both protein expression levels depend on fibroblast growth factor receptor (FGFR) and src signaling. JUNB and FOSB knockdown do not rescue cells from the growth arrest induced by FGF2; however, FOSB knockdown rescue cells from DNA replication delay, indicating that FOSB expression underlies one of the FGF2 antiproliferative effects, namely, S-phase progression delay.

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy

“…Deregulated expression of AP-1 subunits might cause harmful immune cell activation during chronic inflammation and autoimmune diseases [ 51 ]. Previous reports suggest that FOSB and JUNB regulate cell proliferation through various mechanisms [ 52 , 53 ]. Up-regulation of HLA-C, together with down-regulation of cytotoxic effector molecule PRF1, and chemokine CCL4, indicated an impaired function of NK cells in IgAN (Fig.…”

Fgf2 and Ptpn11 play a role in cerebral injury caused by sevoflurane anesthesia

“…However, elevated Fgf2 expression may result in adverse synaptic reconstruction, impacting neural conduction and information transmission. [ 38 ] Brain injury is often accompanied by neural damage, and elevated Ptpn11 expression may interfere with the processes of neural cell proliferation and differentiation, thus affecting the regeneration and repair of neural cells after brain injury. [ 39 ] Numerous research findings demonstrate the interplay between Fgf2, Ptpn11, and sevoflurane anesthesia-induced brain injury, and their expression levels have a significant impact on the prognosis.…”

Profiling of Y1 Cells Treated With FGF-2 Reveals Parallels With Oncogene-Induced Senescence

“…Normalization of phospho-peptides to the levels of their respective proteins is necessary to control for any changes in protein expression that could contribute to a perceived change in phospho-peptide abundance. Since phospho-peptides may also originate from less abundant proteins that lack intensity measurements and only minimal changes in protein abundance are expected at these early timepoints (Bahrami & Drabløs, 2016;Vitorino et al, 2018), we performed a second analysis of phospho-peptide intensities without protein normalization (Supplemental Fig. 7A, Table 6).…”