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Profiling of Y1 cells treated with FGF-2 reveals parallels with oncogene-induced senescence

ABSTRACT: Paradoxically, oncogenes that drive cell cycle progression may also trigger pathways leading to senescence, thereby inhibiting the growth of tumorigenic cells. Along these lines, Y1 cells, which carry an amplification of Ras, become senescent after treatment with the mitogen FGF-2. To understand how FGF-2 promotes senescence, we profiled the epigenome, transcriptome, proteome, and phospho-proteome of Y1 cells stimulated with FGF-2. FGF-2 caused delayed acetylation of histone H4 and higher levels of H3K27me3. Sequencing analysis revealed decreased expression of cell cycle-related genes with concomitant loss of H3K27ac. In contrast, FGF-2 promoted the expression of p21, various cytokines, and MAPK-related genes. Nuclear envelope proteins, particularly lamin B1, displayed increased phosphorylation in response to FGF-2. Proteome analysis suggested alterations in cellular metabolism, as evident by modulated expression of enzymes involved in purine biosynthesis, tRNA aminoacylation, and the TCA cycle. Altogether, the response of Y1 cells to FGF-2 is consistent with oncogene-induced senescence. We propose that Y1 cells enter senescence due to deficient cyclin expression and high levels of p21, which may stem from DNA damage or TGFb signaling.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Peder Lund

LAB HEAD: Benjamin A. Garcia

PROVIDER: PXD020688 | Pride | 2021-06-16

REPOSITORIES: Pride

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			Action	DRS
	20180810_Proteome_FBS.msf	Msf
	20180810_Proteome_FBS_FGF_timecourse.mgf	Mgf
	20180810_Proteome_FBS_FGF_timecourse.mzML	Mzml
	20180810_Proteome_FBS_FGF_timecourse.mzid.gz	Mzid
	20180810_Proteome_FBS_FGF_timecourse_PSMs.txt	Txt

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Profiling of Y1 cells treated with FGF-2 reveals parallels with oncogene-induced senescence

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