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Updated: Jan 17, 2026

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
07:03

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

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TRIM21-mediated ubiquitination of SIX2 attenuates breast cancer stemness via LGSN suppression

Haitao Chen1, Yi Zhou1, Yunnan Zhang2

  • 1School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

Oncogene
|September 15, 2025
PubMed

Insights

The E3 ubiquitin ligase TRIM21 degrades the transcription factor SIX2, reducing breast cancer stemness and metastasis. This TRIM21-SIX2-LGSN pathway offers a new target for breast cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Breast cancer stem cells (BCSCs) drive tumor initiation, metastasis, and resistance to therapy.
  • The transcription factor SIX2 is a key regulator of breast cancer stemness.

Purpose of the Study:

  • To elucidate the regulatory mechanism of SIX2 in breast cancer progression.
  • To investigate the role of TRIM21 in controlling SIX2 stability and function.

Main Methods:

  • Investigated the interaction between TRIM21 and SIX2 using biochemical assays.
  • Analyzed the ubiquitination and degradation of SIX2 mediated by TRIM21.
  • Examined the transcriptional regulation of LGSN by SIX2.
  • Correlated SIX2 and LGSN expression with patient prognosis.

Main Results:

  • TRIM21, an E3 ubiquitin ligase, binds to SIX2 and mediates its K48-linked ubiquitination, leading to proteasomal degradation.
  • SIX2 directly activates LGSN expression, promoting stemness and metastasis.
  • TRIM21-induced SIX2 degradation suppresses LGSN expression, thereby inhibiting breast cancer stemness and metastasis.
  • Elevated SIX2 and LGSN expression correlates with poor patient prognosis.

Conclusions:

  • The TRIM21-SIX2-LGSN axis is a critical regulator of breast cancer progression, stemness, and metastasis.
  • TRIM21 acts as a tumor suppressor by degrading SIX2 and inhibiting LGSN-driven oncogenesis.
  • Targeting the TRIM21-SIX2-LGSN pathway may offer a novel therapeutic strategy for breast cancer.

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