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CALB2 is a mechanoresistance gene in metastatic prostate cancer

GSE337264 Homo sapiens (human) RNA-seq (gene expression) 27 samples Submitted 2026/07/20 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 27 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
Prostate cancerThis series is part of our curated briefing on it.
Samples
27 samples: 9 conditions, mostly in triplicateGroups 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.
Summary (written by the submitters)
Metastatic progression hinges on the ability of circulating tumor cells (CTCs) to withstand the extreme mechanical forces of the bloodstream, yet the mechanisms that enable this survival remain poorly defined. Understanding how prostate cancer (PCa) cells adapt to fluid shear stress (FSS) is essential for identifying vulnerabilities that could be leveraged to prevent metastatic spread.
Read the full summary ↓
Here, we generate “mechanoresistant” (MR) LNCaP and PC3 PCa cell lines by repeatedly exposing cells to high‑intensity (HI) FSS (3950 dyn/cm²), modeling the forces encountered by CTCs in circulation. LNCaP MR cells acquire marked resistance to HI FSS, exhibiting significantly reduced apoptosis compared to controls, while PC3 cells demonstrate a more innate resistance. Morphologically, PC3 MR cells adopt an amoeboid phenotype, whereas LNCaP MR cells retain parental characteristics. Both MR populations show significantly increased Piezo1 expression. Bulk RNA‑sequencing reveals that LNCaP and PC3 MR cells developed distinct molecular programs. Notably, CALB2 (calretinin) emerges as a mechanoresistance gene selectively upregulated in PC3 MR cells, and CALB2 knockout significantly reduces viability upon re‑exposure to HI FSS. Analysis of CALB2‑high PCa cases capture patient‑level molecular heterogeneity, with reproducible co‑expression correlated with EPB41L3 and DGKI, suggesting a mechanoadaptive state rather than a uniform aggressiveness-driven tumor phenotype. This is consistent with the absence of correlation between CALB2 levels and Gleason Scores. In an orthotopic PCa mouse model, the PC3 MR condition displays the most aggressive early tumor growth and the largest endpoint tumor volumes, consistent with enhanced proliferation observed in vitro. Together, these findings demonstrate that PCa cells acquire discrete mechanoadaptive phenotypes under extreme shear stress, revealing targetable pathways that may ultimately be exploited to limit metastatic competence.
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 GSE337264_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 PRJNA1484595 and SRA study SRP714382. Searching any of these in the dataset finder brings you back here.

Study design
9 conditions, mostly in triplicate
LNCaP, Parental, ×3 LNCaP, MR-young, ×3 LNCaP, MN, ×3 LNCaP, MR, ×3 LNCaP, MR* (Unsheared), ×3 PC3, Parental, ×3 PC3, MN, ×3 PC3, MR, ×3 +1 more

Supports a between-group comparison across 27 samples.

How we read this: 9 replicated groups read from 27 sample titles; they account for 27 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
More Prostate cancer datasets

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