Related Experiment Video
Updated: Aug 5, 2025
07:01
Induction and Testing of Hypoxia in Cell Culture
Published on: August 12, 2011
85.1K
Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells
Raefa Abou Khouzam1, Mohak Sharda2,3, Shyama Prasad Rao4
1Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab Emirates.
Frontiers in Cell and Developmental Biology
|March 27, 2023
Summary
Chronic hypoxia in tumors increases cancer cell mutations and genomic instability. This adaptation involves metabolic reprogramming and altered gene expression, highlighting potential therapeutic targets for hard-to-treat cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Tumor microenvironments often experience hypoxia, promoting cancer progression.
- Understanding cellular adaptation to hypoxia is crucial for cancer therapy.
Purpose of the Study:
- Investigate the effects of prolonged hypoxia on cancer cell transcriptional changes, tumor mutational burden (TMB), and genomic instability.
- Differentiate responses based on inherent hypoxia sensitivity.
Main Methods:
- Classified cancer cells into hypoxia-high (HH) and hypoxia-low (HL) groups using a hypoxia score.
- Employed whole exome sequencing and microarray analysis.
Main Results:
- Hypoxia-sensitive (HH) cells exhibited significantly higher TMB and copy number losses.
- Cells adapted by altering gene expression in metabolism and proliferation, increasing alternative splicing, and accumulating mutations.
- High TMB cells showed downregulated DNA replication, repair, and chromosomal maintenance pathways.
Conclusions:
- Chronic hypoxia drives cancer cell survival through metabolic reprogramming, proliferation modulation, and increased genomic instability.
- Identified a 16-gene hypoxia response signature potentially targetable for cancer treatment.
Keywords:
chronic hypoxiacopy number variationgenomic instabilityhypoxiasolid tumorstranscriptome remodelingtumor mutational burdenMore Related Videos
Related Concept Videos
02:53Adaptive Mechanisms in Cancer Cells
5.9K
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,...
5.9K
01:37Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
02:21Cancers Originate from Somatic Mutations in a Single Cell
12.4K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.4K
01:33Cancer-Critical Genes I: Proto-oncogenes
9.1K
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...
9.1K
01:06Induced Pluripotent Stem Cells
4.2K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.2K
02:18Cancer
49.0K
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
49.0K