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RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer

Hiroaki Kajiho1, Yuko Kajiho2, Emanuela Frittoli1

  • 1IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.

EMBO Reports
|June 4, 2016
PubMed

Insights

Researchers identified RAB2A, a protein crucial for ER-to-Golgi transport, as a key driver of breast cancer (BC) cell invasion and dissemination. Elevated RAB2A predicts BC recurrence, highlighting its potential as a therapeutic target.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor cell dissemination mechanisms remain unclear.
  • The role of membrane trafficking in cancer progression is not well understood.

Purpose of the Study:

  • To investigate the role of RAB GTPases in breast cancer cell dissemination.
  • To identify novel molecular determinants of breast cancer invasion.

Main Methods:

  • Functional siRNA screening of human RAB GTPases.
  • Analysis of RAB2A expression and amplification in human breast cancer samples.
  • Investigated RAB2A's interaction with VPS39 and its role in MT1-MMP and E-cadherin trafficking.

Main Results:

  • RAB2A is essential for breast cancer cell proteolytic activity and 3D invasiveness.
  • RAB2A is amplified and elevated in breast cancer, predicting disease recurrence.
  • RAB2A regulates MT1-MMP trafficking via the HOPS complex and E-cadherin transport from the Golgi.

Conclusions:

  • RAB2A is a novel determinant of membrane trafficking essential for breast cancer cell invasion.
  • RAB2A controls key steps in the mesenchymal invasive program of breast cancer dissemination.
  • Targeting RAB2A may offer a new strategy for treating breast cancer recurrence.
Keywords:
RAB GTPasesRAB2Acancer migration and invasionmembrane trafficking

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