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| Status |
Public on Jun 13, 2023 |
| Title |
PCBP1 regulates LIFR through FAM3C to maintain BCSC self-renewal and invasiveness |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The poly(rC) binding protein 1 gene (PCBP1) encodes the heterogenous nuclear ribonucleoprotein E1 (hnRNPE1), a nucleic acid binding protein that plays a tumor-suppressive role in mammary epithelium by regulating phenotypic plasticity and cell fate. Following loss of PCBP1 function, the FAM3C gene (encoding the Interleukin-like EMT inducer, or “ILEI” protein) and the leukemia inhibitory factor receptor (LIFR) gene are upregulated.
Interaction between FAM3C and LIFR in the extracellular space induces phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3). The overexpression and/or hyperactivity of STAT3 has been detected in 40% of breast cancer cases and is associated with poor prognosis. Herein, we characterize feed-forward regulation of LIFR expression in response to FAM3C/LIFR/pSTAT3 signaling in mammary epithelial cells, and show that PCBP1 upregulates LIFR transcription through FAM3C, involving activity at the LIFR promoter.
Additionally, our bioinformatic analysis reveals a signature of transcriptional regulation associated with FAM3C/LIFR interaction and identifies the TWIST1 transcription factor as a downstream effector that participates in maintenance of LIFR expression.
Finally, we characterize the effect of LIFR expression in cell-based experiments that demonstrate promotion of invasion, migration, and breast cancer stem cell (BCSC) self-renewal, consistent with previous studies that link LIFR expression to tumor initiation and metastasis in mammary epithelial cells.
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| Overall design |
Comparative gene expression profiling of bulk RNA extracts from pooled cell populations. Comparisons made between normal murine mammary gland cells (NMuMG) and derivative cell lines, using two independent datasets.
Dataset 1: compares (A) NMuMG shPCBP1 with (B) NMuMG shPCBP1 FAM3C KO and (A) with (C) NMuMG shPCBP1 LIFR KO
Dataset 2: A pre-existing dataset that compares (D) NMuMG with (E) NMuMG shPCBP1
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| Contributor(s) |
Streitfeld W, Dalton A, Howley B, Howe P |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jun 13, 2023 |
| Last update date |
Jun 23, 2023 |
| Contact name |
William Scott Streitfeld |
| E-mail(s) |
streitfe@musc.edu
|
| Phone |
9044774948
|
| Organization name |
Medical University of South Carolina
|
| Department |
Biochemistry and Molecular Biology
|
| Lab |
Philip H. Howe
|
| Street address |
173 Ashley Ave BSB 510
|
| City |
Charleston |
| State/province |
SC |
| ZIP/Postal code |
29425 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (15)
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| GSM7476163 |
Dataset 1: NMuMG shPCBP1 |
| GSM7476164 |
Dataset 1: NMuMG shPCBP1 LIFR KO cell line clone #3 |
| GSM7476165 |
Dataset 1: NMuMG shPCBP1 FAM3C/LIFR Double KO |
| GSM7476166 |
Dataset 1: NMuMG shPCBP1 CT cell line clone #1 |
| GSM7476167 |
Dataset 1: NMuMG shPCBP1 CT cell line clone #2 |
| GSM7476168 |
Dataset 1: NMuMG shPCBP1 CT cell line clone #3 |
| GSM7476169 |
Dataset 1: NMuMG shPCBP1 FAM3C KO cell line clone #1 |
| GSM7476170 |
Dataset 1: NMuMG shPCBP1 FAM3C KO cell line clone #2 |
| GSM7476171 |
Dataset 1: NMuMG shPCBP1 FAM3C KO cell line clone #3 |
| GSM7476172 |
Dataset 1: NMuMG shPCBP1 LIFR KO cell line clone #1 |
| GSM7476173 |
Dataset 1: NMuMG shPCBP1 LIFR KO cell line clone #2 |
| GSM7476174 |
Dataset 2: NMuMG shPCBP1 replicate #1 |
| GSM7476175 |
Dataset 2: NMuMG shPCBP1 replicate #2 |
| GSM7476176 |
Dataset 2: NMuMG replicate #1 |
| GSM7476177 |
Dataset 2: NMuMG replicate #2 |
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| Relations |
| BioProject |
PRJNA983496 |
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