Abstract 889: NF-κB-mediated mitophagy contributes to the maintenance of cancer stem cells in ovarian cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 82; no. 12_Supplement; p. 889
• Main Authors: Li, Na, Pal, Tejinder, Cai, Shurui, Banerjee, Ananya, Bai, Xuetao, Lavudi, Kousalya, Wang, Qi-En
• Format: Journal Article
• Language: English
• Published: 15-06-2022
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2022-889

Abstract
Tumors contain phenotypically and functionally heterogeneous cancer cells. Among them, a minority of cell subpopulation, termed cancer stem cells (CSCs), which possess the self-renewal capacity and are able to generate the heterogeneous lineage of cancer cells, has been believed to be responsible for the initiation and progression of the tumor. However, it is still unclear how the stemness properties of CSCs are maintained in the tumor. Mitophagy is a process by which damaged mitochondria are cleared via autophagy. The significance of mitophagy in the maintenance of CSC has been investigated in multiple CSC types. Our recent study shows that ovarian CSCs also exhibit enhanced mitophagy, which is mainly attributed to elevated expression of mitophagy receptors BNIP3 and BNIP3L. Downregulation of BNIP3 or BNIP3L significantly diminished mitophagy in ovarian CSCs and compromised their self-renewal capability. Mechanistic investigation further revealed that enhanced NF-κB signaling contributes to the increased expression of BNIP3 and BNIP3L. Inhibition of NF-κB signaling pathway via p65 knockdown or specific inhibitors is able to reduce mitophagy in ovarian CSCs. In summary, our data suggest that selective inhibition of NF-κB is able to deplete CSCs by interfering with mitochondria quality control in these cells and has potential to prevent tumor relapse and metastasis.
Citation Format: Na Li, Tejinder Pal, Shurui Cai, Ananya Banerjee, Xuetao Bai, Kousalya Lavudi, Qi-En Wang. NF-κB-mediated mitophagy contributes to the maintenance of cancer stem cells in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 889.