Related Experiment Video
Updated: Jun 6, 2026
09:37
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Two novel human NUMB isoforms provide a potential link between development and cancer
Aldona Karaczyn1, Mahmud Bani-Yaghoub, Roger Tremblay
1Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
Neural Development
|December 3, 2010
Summary
Two new NUMB isoforms, NUMB5 and NUMB6, were identified. They are linked to cancer and alter cell migration by interacting with CDC42 and affecting NOTCH signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- The NUMB protein regulates cell polarity and fate by antagonizing NOTCH signaling.
- Four human NUMB isoforms have been previously identified, each with distinct functions.
Purpose of the Study:
- To identify and characterize novel human NUMB isoforms.
- To investigate the role of these new isoforms in cell migration and cancer.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and luciferase assays to assess NOTCH signaling antagonism.
- Immunocytochemistry to analyze protein interactions.
- Ectopic expression studies to observe effects on cell morphology and migration.
- In vitro and in vivo migration assays.
Main Results:
- Two novel NUMB isoforms, NUMB5 and NUMB6, lacking exon 10, were identified.
- NUMB5 and NUMB6 exhibit reduced antagonism of NOTCH signaling compared to other isoforms.
- These isoforms interact with CDC42, vimentin, and IQGAP1.
- Ectopic expression of NUMB5 and NUMB6 induces lamellipodia and filopodia formation, respectively, in a CDC42- and RAC1-dependent manner.
- NUMB5 and NUMB6 alter cell migratory behavior.
Conclusions:
- NUMB5 and NUMB6 represent novel regulators of cell polarity and migration.
- Their altered interaction with NOTCH signaling and association with CDC42 suggest a role in cancer progression.
- These findings provide new insights into NUMB function in development and disease.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
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...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...