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ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells.
- Source :
- Thoracic Cancer; Aug2022, Vol. 13 Issue 15, p2235-2247, 13p
- Publication Year :
- 2022
-
Abstract
- Background: Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. Methods: LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP. Results: ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar. Conclusion: Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP. [ABSTRACT FROM AUTHOR]
- Subjects :
- ENZYME metabolism
PROTEIN metabolism
WOUND healing
FLOW cytometry
STAINS & staining (Microscopy)
WESTERN immunoblotting
LUNG tumors
CELL motility
CELL survival
ENZYME-linked immunosorbent assay
CELL lines
POLYMERASE chain reaction
REACTIVE oxygen species
CARRIER proteins
HYPOXEMIA
DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 17597706
- Volume :
- 13
- Issue :
- 15
- Database :
- Complementary Index
- Journal :
- Thoracic Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 158341546
- Full Text :
- https://doi.org/10.1111/1759-7714.14552