Back to Search
Start Over
Inhibition of arachidonate lipoxygenase12 targets lung cancer through inhibiting EMT and suppressing RhoA and NF-κB activity.
- Source :
-
Biochemical & Biophysical Research Communications . Apr2020, Vol. 524 Issue 4, p803-809. 7p. - Publication Year :
- 2020
-
Abstract
- The carcinogenic function of arachidonate lipoxygenase12 (Alox12) has been reported in various cancers. However, little is known on the role of Alox12 in lung cancer. Here, we demonstrate that Alox12 is upregulated and contributes to biological activities of lung cancer through multiple mechanisms. We found that Alox12 mRNA and protein levels were increased by 2.5-fold in a panel of lung cancer cell lines compared to normal lung cells. The expression of Alox12 varied among lung cancer cell lines. The immunohistochemistry analysis on paired normal and tumor lung tissues from twenty patients showed that Alox12 protein level is higher in lung cancer than normal lung tissues from the majority of patients. We further observed the upregulation of Alox12-12-HETE signaling axis in lung cancer tissues. Overexpression of Alox12 promoted growth and migration in normal lung cells and lung cancer cells. In contrast, Alox12 inhibition via genetic and pharmacological approaches suppressed growth and migration, induced apoptosis, and sensitized lung cancer cells to chemotherapy. This is through suppressing RhoA signaling, inhibiting epithelial-to-mesenchymal transition (EMT) and NF-κB activity. Our work reveals the therapeutic value of inhibiting Alox12 in overcoming chemoresistance in lung cancer. • Alox12 is elevated in half of lung cancer patients analyzed. • Alox12 overexpression promotes normal and tumor lung cell growth and migration. • Alox12 knockdown inhibits lung cancer cells. • Alox12 depletion suppresses RhoA, EMT and NF-κB activity in lung cancer cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LUNG cancer
*CELL migration
*CANCER cells
*CELL growth
*CANCER chemotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 524
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 142296151
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.01.166