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TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1

Yihua Pang1, Yanan Zhao1, Yan Wang2

  • 1Department of Hematology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.

Journal of Experimental & Clinical Cancer Research : CR
|August 16, 2020
PubMed
Abstract

Insights

Tumor necrosis factor ɑ-induced protein 8 (TNFAIP8) promotes acute myeloid leukemia (AML) chemoresistance by inhibiting apoptosis and activating the ERK pathway. Suppressing TNFAIP8 offers a potential therapeutic strategy for AML treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chemoresistance is a significant challenge in acute myeloid leukemia (AML) treatment.
  • Evasion of apoptosis is a key mechanism underlying AML chemoresistance.
  • Understanding the molecular drivers of chemoresistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor ɑ-induced protein 8 (TNFAIP8) in AML chemoresistance.
  • To elucidate the molecular mechanisms by which TNFAIP8 contributes to AML progression and drug resistance.

Main Methods:

  • Assessed TNFAIP8 expression in AML patients and cell lines using RT-qPCR and western blots.
  • Investigated TNFAIP8's role in apoptosis, drug sensitivity, and proliferation via functional experiments.
  • Examined TNFAIP8's effect on the ERK signaling pathway and its interaction with Rac1.
  • Evaluated TNFAIP8's impact on AML in murine models.

Main Results:

  • TNFAIP8 expression was upregulated in human AML patients and cell lines.
  • TNFAIP8 protects AML cells from chemotherapy-induced apoptosis and enhances drug resistance.
  • TNFAIP8 sustains ERK signaling pathway activity through interaction with Rac1, promoting leukemia.
  • In vivo studies showed TNFAIP8 suppression reduces leukemia infiltration and improves survival.

Conclusions:

  • TNFAIP8 plays a critical role in AML chemoresistance and progression.
  • TNFAIP8's function in AML highlights its potential as a therapeutic target.
Keywords:
AMLApoptosisChemoresistanceERKRac1TNFAIP8

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