2. Academic Validation
  3. LACTB suppresses liver cancer progression through regulation of ferroptosis

LACTB suppresses liver cancer progression through regulation of ferroptosis

  • Redox Biol. 2024 Sep:75:103270. doi: 10.1016/j.redox.2024.103270.
Kaixuan Zeng 1,  Na Huang 2,  Nanbin Liu 3,  Xi Deng 3,  Yanhua Mu 4,  Xurui Zhang 4,  Jian Zhang 5,  Chongyu Zhang 2,  Yong Li 4,  Zongfang Li 6
Affiliations

Affiliations

  • 1 Department of Geriatric Hepatobiliary, Pancreatic and Spleen Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Tumor and Immunology Center of Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • 2 National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Tumor and Immunology Center of Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Shaanxi International Cooperation Base for Inflammation and Immunity, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • 3 Department of Geriatric Hepatobiliary, Pancreatic and Spleen Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • 4 National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Tumor and Immunology Center of Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • 5 Department of Geriatric Hepatobiliary, Pancreatic and Spleen Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Tumor and Immunology Center of Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
  • 6 Department of Geriatric Hepatobiliary, Pancreatic and Spleen Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Tumor and Immunology Center of Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China; Shaanxi International Cooperation Base for Inflammation and Immunity, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China. Electronic address: lzf2568@xjtu.edu.cn.
PMID: 39047638 DOI: 10.1016/j.redox.2024.103270
Abstract

Ferroptosis, driven by iron-dependent phospholipid peroxidation, is emerging as an intrinsic Cancer defense mechanism. However, the regulatory networks involved in Ferroptosis remain largely unknown. Here, we found that serine beta-lactamase-like protein (LACTB) inhibits liver Cancer progression by regulating Ferroptosis. LACTB is downregulated in liver Cancer, and the ectopic expression of LACTB markedly inhibits cell viability, colony formation, and tumour growth. LACTB knockout exerts the opposite effects. Further investigation revealed that LACTB blocks HSPA8 transcription in a p53-dependent manner, resulting in the elevation of NCOA4-mediated ferritinophagy and inhibition of SLC7A11/GSH/GPX4 signalling, thereby triggering Ferroptosis and suppressing liver Cancer progression. Liver Cancer cells with an endogenous mutation of p53 binding site in the HSPA8 promoter exhibited increased resistance to Ferroptosis inducers, and the ferroptosis-promoting effect of LACTB was significantly weakened in these mutant cells. Importantly, LACTB is identified as a downstream target of lenvatinib, and adeno-associated virus-mediated overexpression and knockdown of LACTB notably enhance and attenuate the anti-tumour efficacy of lenvatinib in vivo, respectively. Taken together, our study reveals a novel action of LACTB and provides potential therapeutic strategies for enhancing the efficacy of lenvatinib in liver Cancer.

Keywords

Ferroptosis; LACTB; Lenvatinib; Liver cancer.

Figures
Products
Inhibitors & Agonists
Other Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z