Related Experiment Video
Updated: Jul 1, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis
Yu Zhang1,2, Xiaoyu Ji3, Yu Wang1,2
1Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
Anoikis presents a significant barrier in the metastasis of cancer. As the most aggressive type of thyroid cancer, anaplastic thyroid cancer (ATC) exhibits a high risk of metastasis and is characterized by high mortality. Therefore, investigating the molecular mechanisms of anoikis resistance in ATC is important for devising therapeutic targets in clinical research.
Methods:
Differentially Expressed Genes were screened in ATC cells under attached and detached culture conditions with RNA-seq. Investigate the impact of enolase 2 (ENO2) on apoptosis and spheroid formation by gain and loss of function. Changes of reactive oxygen species (ROS), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were detected to assess redox balance. The transcriptional regulatory role of signal transducer and activator of transcription 1 (STAT1) on ENO2 was validated through Dual-Luciferase Reporter Gene Assay. Explore the impact of ENO2 expression on the formation of lung metastases in nude mice.
Results:
We found that the glycolysis process was activated in detached ATC cells. Several genes in the glycolysis process, particularly ENO2, a member of the enolase superfamily was upregulated in ATC cells cultured in suspension. The upregulation of ENO2 enabled the maintenance of redox balance by supplying GSH and NADPH, thereby preventing cells from undergoing anoikis. In terms of mechanism, the expression of STAT1 was enhanced in anoikis resistance cells, which in turn positively regulated the expression of ENO2. In vivo, ENO2-suppressed ATC cells resulted in a significantly lower rate of lung colonization compared to control ATC cells.
Conclusions:
Stable expression of ENO2 and the maintenance of redox balance played a pivotal role in facilitating anoikis resistance of ATC.
Insights
Anaplastic thyroid cancer cells resist anoikis through enolase 2 (ENO2) and redox balance, hindering metastasis. Suppressing ENO2 reduces lung colonization in vivo, offering therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Anoikis, or anchorage-dependent cell death, is a critical barrier to cancer metastasis.
- Anaplastic thyroid cancer (ATC) is highly aggressive, with significant metastatic potential and mortality.
- Understanding anoikis resistance mechanisms in ATC is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the role of enolase 2 (ENO2) in anoikis resistance in anaplastic thyroid cancer.
- To elucidate the molecular mechanisms underlying ENO2-mediated anoikis resistance.
- To evaluate the therapeutic potential of targeting ENO2 in ATC metastasis.
Main Methods:
- RNA-sequencing to identify differentially expressed genes in attached vs. detached ATC cells.
- Gain and loss-of-function studies to assess ENO2's impact on apoptosis and spheroid formation.
- Measurement of reactive oxygen species (ROS), glutathione (GSH), and NADPH to evaluate redox balance.
- Dual-luciferase reporter assays to validate STAT1's transcriptional regulation of ENO2.
- In vivo studies in nude mice to assess the effect of ENO2 suppression on lung metastasis.
Main Results:
- ENO2 was significantly upregulated in detached ATC cells, correlating with activated glycolysis.
- ENO2 overexpression maintained redox balance by supplying GSH and NADPH, conferring anoikis resistance.
- Signal transducer and activator of transcription 1 (STAT1) positively regulated ENO2 expression in anoikis-resistant cells.
- Suppression of ENO2 in ATC cells significantly reduced lung colonization in vivo.
Conclusions:
- Stable ENO2 expression is pivotal for anoikis resistance in anaplastic thyroid cancer.
- Maintaining redox balance through ENO2 is a key mechanism facilitating ATC metastasis.
- Targeting ENO2 presents a promising therapeutic avenue for controlling ATC progression and metastasis.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:30Apoptosis
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...