GEO series

PI3K regulates TAZ/YAP and mTORC1 and can synergistically be targeted in sarcomas

GSE274982 Mus musculus (mouse) RNA-seq (gene expression) 25 samples Submitted 2024/10/01 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 25 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 25 samples
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.

Summary (written by the submitters)

Sarcomas encompass heterogenous, difficult to treat cancers, lacking common therapeutic targets. Phosphatidylinositol-3 kinase (PI3K) signaling is activated in sarcomas to a greater degree than previously appreciated due to phosphatase and tensin homolog (PTEN) loss, and could represent such a target. Targeting PI3K signaling has largely focused on targeting mTORC1, considered the main effector of PI3K signaling, but this has not translated to success in the clinic, suggesting that there may be other effectors downstream of PI3K.

Read the full summary ↓

One gap in our understanding of the PI3K signaling pathway has been the absence of a known oncogenic transcription factor. Herein we implicate TAZ and YAP as additional transcriptional effectors downstream of PI3K signaling regulated by a LATS1/2 dependent mechanism. Using in vitro and in vivo approaches, we show that TAZ and YAP are central oncoproteins in PI3K driven oncogenesis along with mTORC1, providing a rationale for combination therapy. Leveraging these findings, we describe a therapeutic approach that builds upon pre-existing therapeutic strategies utilizing mTORC1 inhibitors and combines them with new TEAD inhibitors that target YAP and TAZ. Combination therapy using everolimus and IK-930, an inhibitor targeting autopalmitoylation of the TEADs, synergistically diminished proliferation and anchorage dependent growth of PI3K activated sarcoma cell lines at low, physiologically achievable doses. In vivo, this combination therapy showed a synergistic effect, contrasting with the lack of effect of the individual single agent therapies, suggesting that an integrated view of PI3K and Hippo signaling can be leveraged therapeutically in PI3K activated sarcomas.

This dataset

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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 GSE274982_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1148673 and SRA study SRP526738. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 25 more — browse all 25 samples with per-sample file links →

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GSE275614 Single-nucleus-RNA-sequencing data from isolated glomeruli from 4-week-old podocyte-specific YAP or TAZ knockout mice 8 samples shares taz, yap
GSE277188 Decoding the YAP/TAZ–PPARγ Regulatory Axis in Adipocyte Differentiation and Dedifferentiation [ChIP-seq] 46 samples shares taz, yap
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