2. Academic Validation
  3. Inhibition of ABI2 ubiquitination-dependent degradation suppresses TNBC cell growth via down-regulating PI3K/Akt signaling pathway

Inhibition of ABI2 ubiquitination-dependent degradation suppresses TNBC cell growth via down-regulating PI3K/Akt signaling pathway

  • Cancer Cell Int. 2024 Jun 27;24(1):222. doi: 10.1186/s12935-024-03407-0.
Linlin Lv 1 2,  Shujing Li 1,  Jie Kang 1,  Yulin Li 1,  Nannan Zhao 3,  Dongman Ye 3,  Fengying Qin 3,  Jing Sun 4,  Tao Yu 5,  Huijian Wu 6
Affiliations

Affiliations

  • 1 School of Bioengineering & Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning Province, 116024, China.
  • 2 Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
  • 3 Cancer Hospital of Dalian University of Technology, Shenyang, 110042, China.
  • 4 Cancer Hospital of Dalian University of Technology, Shenyang, 110042, China. sunjing_mdw@sina.com.
  • 5 Cancer Hospital of Dalian University of Technology, Shenyang, 110042, China. yutao@cancerhosp-ln-cmu.com.
  • 6 School of Bioengineering & Key Laboratory of Protein Modification and Disease, Dalian University of Technology, Dalian, Liaoning Province, 116024, China. wuhj@dlut.edu.cn.
PMID: 38937761 DOI: 10.1186/s12935-024-03407-0
Abstract

Triple negative breast Cancer (TNBC) is a type of Cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 Ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell Apoptosis, making it a promising candidate for impeding the progression of TNBC.

Keywords

ABI2; CBLC; Colistimethate sodium; PI3K/Akt; TNBC.

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