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Updated: Oct 7, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.4K

RNF12 is regulated by AKT phosphorylation and promotes TGF-β driven breast cancer metastasis

Yongsheng Huang1,2, Sijia Liu3, Mengjie Shan4

  • 1Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yongsheng@ibms.pumc.edu.

Cell Death & Disease
|January 11, 2022
PubMed

Insights

High RNF12 expression promotes breast cancer metastasis by enhancing TGF-β signaling via AKT. RNF12 overexpression correlates with poor prognosis and invasiveness in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Transforming growth factor-β (TGF-β) is a key driver of metastasis in advanced breast cancer.
  • RNF12, an E3 ubiquitin ligase, enhances TGF-β signaling by degrading SMAD7, but its regulation and role in cancer remain unclear.

Purpose of the Study:

  • To investigate the role of RNF12 in breast cancer progression and its regulation by AKT signaling.
  • To elucidate the mechanistic link between RNF12, AKT, and TGF-β pathways in breast cancer metastasis.

Main Methods:

  • Analysis of RNF12 expression in human breast cancer tissues and correlation with prognosis.
  • In vitro studies using breast cancer cell lines to assess migration, invasion, and metastasis.
  • Zebrafish and murine xenograft models for experimental metastasis.
  • Western blotting and immunofluorescence to determine protein levels, localization, and interactions.

Main Results:

  • RNF12 is overexpressed in invasive breast cancers, correlating with poor prognosis.
  • High RNF12 expression promotes breast cancer cell migration, invasion, and metastasis in vivo.
  • AKT-mediated phosphorylation of RNF12 enhances its stability, nuclear localization, and SMAD7 degradation.
  • RNF12 and AKT signaling pathways cooperate in promoting breast cancer cell migration.
  • RNF12 expression correlates with phosphorylated AKT and SMAD2 in patient tissues.

Conclusions:

  • RNF12 is a critical mediator of breast cancer progression and metastasis.
  • The AKT-mediated regulation of RNF12 highlights a crucial crosstalk between AKT and TGF-β signaling.
  • RNF12 represents a potential therapeutic target for aggressive breast cancer subtypes.

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