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DAPK2 activates NF-κB through autophagy-dependent degradation of I-κBα during thyroid cancer development and

Yan Jiang1, Ji Liu2, Hua Xu3

  • 1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Annals of Translational Medicine
|August 23, 2021
PubMed
Abstract

Insights

Death-associated protein kinase 2 (DAPK2) promotes thyroid cancer growth and resistance to TRAIL-induced apoptosis. Inhibiting DAPK2 may offer a new therapeutic strategy for thyroid cancer by disrupting autophagy and NF-κB signaling.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Death-associated protein kinase 2 (DAPK2) is a serine/threonine kinase involved in autophagy and apoptosis, acting as a tumor suppressor in many cancers.
  • The specific role of DAPK2 in thyroid cancer (TC) pathogenesis remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the function of DAPK2 in thyroid cancer development and progression.
  • To investigate the molecular mechanisms underlying DAPK2's role in TC, including its impact on cell proliferation, apoptosis, and autophagy.

Main Methods:

  • Differential gene expression analysis using RNA sequencing on human TC samples.
  • Quantitative real-time polymerase chain reaction (qRT-PCR) to validate DAPK2 mRNA expression.
  • Functional studies involving DAPK2 knockdown and overexpression in a TTA1 cell line to assess effects on proliferation, apoptosis, autophagy, and NF-κB activation.

Main Results:

  • DAPK2 was found to be upregulated in thyroid cancer tissues.
  • DAPK2 knockdown suppressed cell proliferation, enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, and restricted tumor growth.
  • DAPK2 promoted autophagy and NF-κB activation via autophagy-mediated I-κBα degradation, contributing to tumor growth and apoptosis resistance.

Conclusions:

  • DAPK2 plays a critical role in thyroid carcinogenesis, supporting tumor growth and resistance to TRAIL-induced apoptosis.
  • The mechanism involves DAPK2-mediated autophagy and subsequent NF-κB activation through I-κBα degradation.
  • DAPK2 represents a potential novel therapeutic target for thyroid cancer treatment.
Keywords:
Death-associated protein kinase 2 (DAPK2)I-κBαautophagynuclear factor-κB (NF-κB)thyroid cancer (TC)

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