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Abnormally localized DLK1 interacts with NCOR1 in non-small cell lung cancer cell nuclear

Jinjing Tan1,2, Susu Zhang3,4, Lin Li5

  • 1Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.

Bioscience Reports
|October 30, 2019
PubMed

Insights

Delta-like homolog 1 (DLK1) was found in the nucleus of lung cancer cells, interacting with NCOR1. This nuclear DLK1 and NCOR1 interaction may regulate cell differentiation and offers prognostic potential in non-small cell lung cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Delta-like homolog 1 (DLK1) functions as a ligand in the Notch signaling pathway and is implicated in tumorigenesis.
  • The dual behavior of DLK1 in different cell types is attributed to its known isoforms, but these do not fully explain observed phenomena.
  • Previous research suggests DLK1's role in cell proliferation and signaling activation is context-dependent and sometimes contradictory.

Purpose of the Study:

  • To investigate the subcellular localization of DLK1 in lung cancer.
  • To identify novel interaction partners of DLK1 within the cell.
  • To explore the functional and prognostic significance of DLK1 and its interaction partners in non-small cell lung cancer (NSCLC).

Main Methods:

  • Immunohistochemistry (IHC) to detect nuclear DLK1 in NSCLC patient samples.
  • Co-immunoprecipitation (co-IP) followed by mass spectrometry (MS) to identify DLK1 interacting proteins.
  • Analysis of NCOR1 expression in independent patient cohorts and assessment of its prognostic value.

Main Results:

  • Nuclear localization of DLK1 was confirmed in a subset of NSCLC samples and correlated with tissue differentiation and tumor size.
  • Nuclear receptor corepressor 1 (NCOR1) was identified as a novel nuclear interaction partner of DLK1.
  • NCOR1 demonstrated tumor suppressor activity and prognostic potential in lung squamous carcinomas, with evidence of colocalization with nuclear DLK1.

Conclusions:

  • DLK1 exhibits nuclear localization in lung cancer cells, suggesting a role beyond its known secreted or membrane-bound forms.
  • The interaction between nuclear DLK1 and NCOR1 represents a novel molecular mechanism potentially involved in regulating cell differentiation in NSCLC.
  • NCOR1 serves as a potential tumor suppressor and prognostic biomarker in lung squamous cell carcinoma, possibly mediated through its interaction with nuclear DLK1.
Keywords:
DLK1NCOR1non-small-cell lung cancernotch signalling pathwaynuclear localizationprotein-protein interactions

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