2. Academic Validation
  3. The deubiquitinase OTUD5 stabilizes SLC7A11 to promote progression and reduce paclitaxel sensitivity in triple-negative breast cancer

The deubiquitinase OTUD5 stabilizes SLC7A11 to promote progression and reduce paclitaxel sensitivity in triple-negative breast cancer

  • Cancer Lett. 2024 Nov 1:604:217232. doi: 10.1016/j.canlet.2024.217232.
Xizhi Liu 1,  Zhiqiang Ma 2,  Xin Jing 3,  Guanying Wang 4,  Lin Zhao 5,  Xinhan Zhao 6,  Yujiao Zhang 7
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2 Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Xi'an, China.
  • 3 Department of Pathology, Shaanxi Provincial People's Hospital, Xi'an, China.
  • 4 Department of Medical Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 6 Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: zhaoxinhan@mail.xjtu.edu.cn.
  • 7 Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: yujiaozhang_123@163.com.
PMID: 39276913 DOI: 10.1016/j.canlet.2024.217232
Abstract

Ferroptosis is a newly defined form of programmed cell death characterized by iron-dependent lipid peroxide accumulation and is associated with the progression of Cancer. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate antiporter, has been characterized as a critical regulator of Ferroptosis. Although many studies have established the transcriptional regulation of SLC7A11, it remains largely unknown how the stability of SLC7A11 is regulated in cancers, especially in triple-negative breast Cancer (TNBC). Here we demonstrated that ovarian tumor domain-containing protein 5 (OTUD5), which deubiquitinated and stabilized SLC7A11, played a key role in TNBC progression and paclitaxel chemosensitivity through modulating Ferroptosis. The clinical data analysis showed OTUD5 was higher expressed in TNBC, which positively correlated with SLC7A11 level. Mechanistically, OTUD5 interacted with SLC7A11 and cleaved K48-linked polyubiquitin chains from SLC7A11 to enhance the stability of SLC7A11. Taken together, these findings uncover a functional and mechanistic role of OTUD5 in TNBC progression and paclitaxel sensitivity, indicating OTUD5 could be a potential target for TNBC treatment.

Keywords

Ferroptosis; OTUD5; Paclitaxel sensitivity; SLC7A11; Triple-negative breast cancer.

Figures
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