Eribulin induces micronuclei and enhances the nuclear localization of cGAS in triple-negative breast cancer cells.

Autor:	Yamada H; Chiba University., Takada M; Chiba University., Ghone D; University of Wisconsin-Madison., Yu M; Chiba University., Nagashima T; Chiba University., Fujimoto H; Chiba University., Sakakibara J; Chiba University., Hasegawa Y; Hachinohe City Hospital., Takao S; Konan Medical Center., Yamada A; Yokohama City University., Narui K; Yokohama City University Medical Center., Ishikawa T; Tokyo Medical University., Suzuki A; University of Wisconsin-Madison., Otsuka M; Chiba University.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Dec 06. Date of Electronic Publication: 2023 Dec 06.
DOI:	10.21203/rs.3.rs-3672056/v1
Abstrakt:	Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI's effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI's impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies. Competing Interests: Competing interests The authors declare no competing interests. This work was supported by JSPS KAKENHI Grant Number JP22K08727 and JP21K08638
Databáze:	MEDLINE
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