Loss of tumor suppressor p53 upregulates stem cell factor SOX9 via Notch signaling
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Loss of the tumor suppressor p53 promotes basal-like breast cancer (BLBC) progression by upregulating SOX9. This occurs through increased Psen2 expression and Notch1 signaling, driving cell de-differentiation.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- Basal-like breast cancer (BLBC), a subtype of triple-negative breast cancer, exhibits high cellular plasticity due to abundant stem-like cancer cells.
- SOX9, a transcription factor in luminal progenitor cells, is upregulated during BLBC progression, promoting dedifferentiation to stem cell-like states crucial for malignancy.
- The mechanism driving SOX9 upregulation in BLBC remains largely unknown.
Purpose Of The Study
- To investigate the role of p53 loss in SOX9 upregulation during basal-like breast cancer progression.
- To elucidate the molecular mechanisms by which p53 loss influences SOX9 expression and protein stability.
Main Methods
- Utilized primary mammary cell organoids to study the effects of p53 loss.
- Assessed SOX9 expression and protein half-life in response to p53 loss.
- Investigated the involvement of Psen2 and Notch1 signaling pathways.
Main Results
- p53 loss induced SOX9 expression and stabilized its protein half-life in mammary cell organoids.
- p53 loss led to increased Psen2 expression, activating Notch1 signaling.
- Activated Notch1 signaling subsequently induced SOX9 expression.
Conclusions
- Identified a novel molecular mechanism linking p53 loss to SOX9 upregulation in BLBC.
- Demonstrated that p53 loss coopts SOX9 to drive cell de-differentiation, contributing to BLBC malignant progression.
- This finding highlights a potential therapeutic target for BLBC.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...