← BioTransfer GEO Dataset Finder
GEO series

Novel hydrophobic tag degraders overcome endocrine-resistant breast cancer by recruiting HSP27-mediated E3 ligase complex for ERα proteasomal degradation

GSE322892 Homo sapiens (human) RNA-seq (gene expression) 9 samples Submitted 2026/07/29 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 9 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
Homo sapiens (human)
Topic
Breast cancerThis series is part of our curated briefing on it.
Samples
9 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.
Paper
Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal DegradationAngewandte Chemie (International ed. in English) · 2026
Summary (written by the submitters)
Hydrophobic tag (HyT)-mediated protein degradation has emerged as a pivotal tool for targeted protein degradation (TPD), yet its underlying degradation mechanism remains incompletely elucidated. Herein, we designed structurally optimized HyT-based degraders by covalently conjugating hydrophobic amino acid tags to ERα-targeting ligands via alkane linkers of varying lengths, identifying the lead compound VI-10h.
Read the full summary ↓
VI-10h exhibited potent antiproliferative activity and efficient ERα degradation in endocrine-resistant breast cancer cells (LCC2, MCF-7D538G, MCF-7Y537S, and MCF-7EGFR) and superior antitumor activity compared to the clinical drug fulvestrant (Ful) in MCF-7 and tamoxifen-resistant LCC2 xenograft models. To elucidate the HyT-mediated degradation mechanism, we synthesized biotin-conjugated HyTs (biotin-Lys and biotin-Trp) and performed pull-down assays combined with mass spectrometry. Our results unveiled that VI-10h selectively recruits HSP27 as a novel atypical E3 ligase adaptor protein, forms an ERα-HSP27-RING1 ternary complex to promote ERα degradation, disrupts estrogen-dependent oncogenic networks, and circumvents the drug resistance associated with conventional CRBN- or VHL-dependent E3 ligase-recruiting degraders. This study validates HyT technology’s degradation mechanism and feasibility in reversing resistance to conventional E3 ligases and overcoming endocrine-resistant breast cancer, establishing a molecular design strategy for next-generation targeted degraders that reverse endocrine resistance.
Published in
Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal Degradation
Xin L, Song Z, Cui Y et al. · Angewandte Chemie (International ed. in English) 2026 · PMID 42189698 · doi:10.1002/anie.202525741
This dataset
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.

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 GSE322892_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1431973 and SRA study SRP680915. Searching any of these in the dataset finder brings you back here.

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 9 more — browse all 9 samples with per-sample file links →

More Breast cancer datasets

Search all human RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.