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RNA m6A reader IGF2BP3 promotes metastasis of triple-negative breast cancer via SLIT2 repression

Tongtong Jiang1, Xinyi He1, Zhining Zhao2

  • 1State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 17, 2022
PubMed

Insights

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) drives triple-negative breast cancer (TNBC) metastasis by destabilizing SLIT2 mRNA. Targeting IGF2BP3 and RNA modification may offer new TNBC treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with high metastatic potential.
  • Mechanisms driving TNBC metastasis are not fully understood.
  • RNA modifications, like N6-methyladenosine (m6A), play roles in cancer progression.

Purpose of the Study:

  • Investigate the role of IGF2BP3 in TNBC metastasis.
  • Elucidate the molecular mechanisms by which IGF2BP3 influences TNBC cell invasion.
  • Identify potential therapeutic targets for TNBC treatment.

Main Methods:

  • Analysis of IGF2BP3 expression in TNBC patient samples.
  • In vitro studies assessing TNBC cell migration and invasion.
  • Mechanistic studies involving RNA immunoprecipitation and pathway analysis.

Main Results:

  • IGF2BP3 is highly expressed in TNBC and linked to poor survival.
  • IGF2BP3 enhances TNBC cell migration and invasion via m6A modification.
  • IGF2BP3 destabilizes SLIT2 mRNA, impacting PI3K/AKT and MEK/ERK signaling.
  • The IGF2BP3/SLIT2 pathway is crucial for TNBC metastasis in vivo.

Conclusions:

  • IGF2BP3 is a key regulator of TNBC distant metastasis.
  • The IGF2BP3/SLIT2 axis represents a novel regulatory network in breast cancer metastasis.
  • Targeting the m6A machinery, including IGF2BP3, is a promising therapeutic strategy for TNBC.
Keywords:
IGF2BPN6-methyladenosine (m6A)RNA modificationSLIT2breast cancermetastasis

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