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| Status |
Public on Aug 01, 2020 |
| Title |
Paracrine Ras/ERK signalling drives gene expression plasticity in a model of basal-like breast cancer |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The EGFR/Ras/ERK signalling pathway is a primary driver of cancer cell proliferation and metastasis in tumours that exhibit high cell-to-cell heterogeneity. While the signalling activity of this pathway is frequently amplified in tumours, it is not understood how the kinetic aspects of its activation in tumours differ from normal cellular signalling. We explored these single-cell kinetic differences using live-cell reporters of ERK signalling in the breast cancer progression series HMT-3522 and found that ERK activity in invasive cells is similar in amplitude to non-malignant cells but is highly dynamic and more disordered, leading to more heterogeneous expression of ERK target genes. We traced this variability to a high degree of amphiregulin-mediated autocrine signalling by invasive cells. Dynamic ERK activity could be transferred from invasive to pre-malignant cells through paracrine signalling in co-culture, and could drive temporal variation in the expression of genes including Fra-1, c-Myc, and Egr1 at the single-cell level. Our findings establish a mechanism for the generation of tumour cell plasticity, in which paracrine signalling in the microenvironment is translated into continually shifting diversity in gene expression profiles, helping drive the phenotypic heterogeneity of tumour cells.
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| |
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| Overall design |
Drop-seq analysis of HMT-3522 cell culture lines S1, T4 (10,212 cells, 5 samples total including 1 species mixing experiment)
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| Contributor(s) |
Siebert S, Davies AE |
| Citation missing |
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| Submission date |
Aug 08, 2018 |
| Last update date |
Aug 01, 2020 |
| Contact name |
Celina E Juliano |
| E-mail(s) |
cejuliano@ucdavis.edu
|
| Organization name |
University of California Davis
|
| Department |
MCB
|
| Lab |
Julianolab
|
| Street address |
149 Briggs Hall
|
| City |
Davis |
| State/province |
California |
| ZIP/Postal code |
95616 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19415 |
Illumina NextSeq 500 (Homo sapiens; Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA485185 |
| SRA |
SRP156797 |
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