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Coupling of LETM1 up-regulation with oxidative phosphorylation and platelet-derived growth factor receptor signaling

Jandee Lee1, Woo Kyung Lee2, Mi-Youn Seol1

  • 1Department of Surgery, Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

Oncotarget
|August 25, 2016
PubMed

Insights

Mitochondrial calcium transporter LETM1 up-regulation drives aggressive thyroid cancer by activating platelet-derived growth factor (PDGF) signaling pathways, promoting tumor growth and metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cellular proliferation and metabolic reprogramming are key in cancer development.
  • LETM1, a mitochondrial calcium transporter, is implicated in cellular growth signaling.

Purpose of the Study:

  • To investigate the role of LETM1 in thyroid cancer progression.
  • To elucidate the molecular mechanisms linking LETM1 to aggressive tumor phenotypes.

Main Methods:

  • Gene Set Enrichment Analysis (GSEA)
  • Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)
  • Immunoblotting
  • Immunohistochemistry
  • Clinical data analysis

Main Results:

  • LETM1 up-regulation correlates with platelet-derived growth factor (PDGF) receptor and insulin signaling pathways.
  • LETM1 induces YAP1 nuclear accumulation, increasing PDGFB, PDGFRB, and THBS4 expression.
  • LETM1 up-regulation is associated with aggressive thyroid cancer features, including lymphovascular invasion and lymph node metastasis, and predicts increased risk.

Conclusions:

  • LETM1 up-regulation promotes aggressive thyroid cancer phenotypes.
  • LETM1 activates proliferative signaling pathways, including the PDGF pathway, via AKT-induced YAP1 transactivation.
  • LETM1 is a potential biomarker for aggressive thyroid cancer and therapeutic target.
Keywords:
LETM1cell proliferationelectron transport chainmetabolismprognosis

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