GEO series

Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation

GSE301557 Homo sapiens (human) DNA methylation 12 samples Submitted 2025/07/03 Platform GPL34284

At a glance

DNA methylation · human · 12 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Samples: 12 samples: 3 × 293T, -Met+Hcy 12 hr, vs 3 × R1, -Met+Hcy 12 hr, vs 3 × 293T, +Met 12 hr, vs 3 × R1, +Met 12 hr,Groups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell ProliferationBiomolecules · 2025

Summary (written by the submitters)

Cancer cells exhibit a well-documented, yet poorly understood, dependence on exogenous methionine, despite retaining the capacity to convert homocysteine to methionine. In contrast, non-tumorigenic cells can proliferate when methionine is replaced by homocysteine. To investigate the mechanistic basis of this methionine dependence, we examined how methionine metabolism impacts cancer cell proliferation.

Read the full summary ↓

We identified carboxy-methylation of the catalytic subunit of Protein Phosphatase 2A (PP2A) as a critical node linking methionine availability to proliferation. PP2A methylation was found to be highly sensitive to intracellular S-adenosylmethionine (SAM) levels, with reduced methylation correlating with impaired proliferation under methionine restriction. Overexpression of Protein Phosphatase Methylesterase-1 (PME-1), which demethylates PP2A, or expression of a Leu309-deleted PP2A mutant that mimics the demethylated form, was sufficient to reduce proliferation even in methionine-independent cells. These findings support a model in which methionine limitation lowers SAM availability, thereby decreasing PP2A methylation and impairing cell proliferation. Our study reveals a mechanistic link between methionine metabolism and cell proliferation and suggests that PP2A methylation plays a key role in the unique methionine dependence of cancer cells.

Published in

Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation

Andronicos A, Yoneda KC, Lin DW et al. · Biomolecules 2025 · PMID 41008516 · doi:10.3390/biom15091210

This dataset

Open GSE301557 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE301557_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1285445 and SRA study SRP597886. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41008516) ↗

Study design

3 × 293T, -Met+Hcy 12 hr, vs 3 × R1, -Met+Hcy 12 hr, vs 3 × 293T, +Met 12 hr, vs 3 × R1, +Met 12 hr,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9085120 293T, -Met+Hcy 12 hr, 1 293T, -Met+Hcy 12 hr,
GSM9085121 R1, -Met+Hcy 12 hr, 1 R1, -Met+Hcy 12 hr,
GSM9085122 293T, -Met+Hcy 12 hr, 2 293T, -Met+Hcy 12 hr,
GSM9085123 R1, -Met+Hcy 12 hr, 2 R1, -Met+Hcy 12 hr,
GSM9085124 293T, -Met+Hcy 12 hr, 3 293T, -Met+Hcy 12 hr,
GSM9085125 R1, -Met+Hcy 12 hr, 3 R1, -Met+Hcy 12 hr,
GSM9085126 293T, +Met 12 hr, 1 293T, +Met 12 hr,
GSM9085127 R1, +Met 12 hr, 1 R1, +Met 12 hr,
GSM9085128 293T, +Met 12 hr, 2 293T, +Met 12 hr,
GSM9085129 R1, +Met 12 hr, 2 R1, +Met 12 hr,
GSM9085130 293T, +Met 12 hr, 3 293T, +Met 12 hr,
GSM9085131 R1, +Met 12 hr, 3 R1, +Met 12 hr,

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