The effect of cullin 4A on lung cancer cell chemosensitivity to paclitaxel through p33ING1b regulation.
Year: 2021
Type: article
Abstract: Cullin 4A (Cul4A) reportedly has oncogenic roles in several cancer types by regulating tumor suppressors through the ubiquitination and proteolysis of the tumor suppressor. In addition, Cul4A is associated with chemosensitivity to chemotherapy drugs. This study investigated the association between Cul4A and lung cancer cell chemosensitivity to paclitaxel, particularly with respect to the role of the p33 inhibitor of the growth 1 (p33ING1b) tumor suppressor. The results showed that the Cul4A knockdown upregulated the p33ING1b expression in lung cancer cells and increased the lung cancer cell and mice tumor xenograft chemosensitivity to paclitaxel. The Cul4A knockdown also inhibited the growth and increased the apoptosis in the tumor xenografts treated with paclitaxel. Notably, the p33ING1b overexpression increased the lung cancer cell chemosensitivity to paclitaxel, but the p33ING1b knockdown reduced the chemosensitivity. A further analysis demonstrated that Cul4A regulates the expression of p33ING1b through protein-protein interactions, ubiquitination, and protein degradation. In conclusion, the present findings suggest that Cul4A mediates the chemosensitivity of lung cancer cells to paclitaxel by regulating p33ING1b. These findings may offer novel insights into future therapeutic strategies for lung cancer that target Cul4A.
Source: PubMed Central
Institutions: Chang Gung Memorial Hospital, Chiayi Chang Gung Memorial Hospital, Sin-Lau Christian Hospital, Chang Gung University of Science and Technology, Chang Gung University, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Lawrence Berkeley National Laboratory, Taoyuan Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3214106963