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| Status |
Public on Jun 09, 2020 |
| Title |
Luminal Stem Cell Determinant SOX9 Controls Lineage Plasticity and Progression in Basal-Like Breast Cancer (Sox9-KO) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Lineage plasticity plays an important role in the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. Although studies suggest BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal and bipotent phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal/bipotent reprogramming remains unclear. Here we show that the transcription factor SOX9 acts as a determinant for ER– luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical NF-B signaling. Inactivation of p53 and Rb in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-bipotent reprogramming in vivo. SOX9 deletion inhibits the progression of benign, neoplastic lesions to invasive carcinoma. Furthermore, SOX9 is overexpressed and correlated with shorter relapse-free survival in human BLBC. These data show that ER– LSPC determinant SOX9 acts as a lineage-specific driver for BLBC transformation.
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| Overall design |
Mammary glands from three Sox9Fl/Fl animals and thee MMTV-iCre; Sox9Fl/Fl animals, in diestrus, were reduced to a single cell suspension sperately. From the Sox9Fl/Fl animals ER-negative luminal cells (Lin-,EpcamHi,CD49fLo,Sca1-negative) were sorted into Trizol LS. From the MMTV-iCre;Sox9Fl/Fl animals the same gating scheme was used, with the addition of the cells being ECFP+, to sort Sox9-null ER-negative luminal cells into Trizol LS. The resulting RNA was analyzed for gene expression differences by microarray.
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| Contributor(s) |
Christin JR, Guo W |
| Citation(s) |
32521267 |
| |
| Submission date |
Aug 16, 2019 |
| Last update date |
Jun 25, 2020 |
| Contact name |
John Robert Christin |
| Phone |
7186781277
|
| Organization name |
Albert Einstein College of Medicine
|
| Department |
Cell Biology
|
| Lab |
Guo Lab
|
| Street address |
1301 Morris Park Avenue, Room 108/114
|
| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10461 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE135892 |
Luminal Stem Cell Determinant SOX9 Controls Lineage Plasticity and Progression in Basal-Like Breast Cancer |
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| Relations |
| BioProject |
PRJNA560490 |
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