Introduction
Results
LOXL3 mitochondrial localization and enzyme activity endowed liver cancer cells with tolerance toward chemotherapy-induced ferroptosis
a
EGF–EGFR signaling mediated the LOXL3–TOM20 axis, blocking chemotherapy-induced ferroptosis, and upregulating LOXL3 phosphorylation at S704
a
LOXL3 phosphorylation prevents DHODH-K344 ubiquitination and promotes DHODH stability to resist chemotherapy-induced ferroptosis
a
Mitochondrial adenylate kinase 2 phosphorylates LOXL3-S704 and confers resistance to chemotherapy-induced ferroptosis
a
S704D-Loxl3 confers resistance to Oxaliplatin treatment in sleeping beauty transposon-induced liver cancer
a, b
Low-dose Oxaliplatin with LOXL3–DHODH axis inhibition efficiently facilitates treatment in advanced liver cancer
a–e
Loxl3-S704D
The AK2–LOXL3–DHODH axis predicts prognosis, providing a combination strategy for advanced liver cancer
a
Discussion
To explore the association between the LOX family and chemotherapy, we depleted LOX family members individually in these two cell lines and observed LOXL3 depletion sensitized liver cancer cells to chemotherapeutic drugs. Targeting the LOX family is an exciting prospect for the development of new drugs to prevent cancer progression and metastasis. Preclinical studies have examined the targeting of LOX or LOXL2 by small irreversible competitive inhibitors, and the use of specific function-blocking antibodies to prevent metastasis6,27