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Published on: January 6, 2017

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DLC1 is the principal biologically-relevant down-regulated DLC family member in several cancers

Dunrui Wang1, Xiaolan Qian1, Megha Rajaram1,2

  • 1Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Oncotarget
|May 14, 2016
PubMed

Insights

Reduced expression of Deleted in Liver Cancer 1 (DLC1) is common in many cancers, impacting patient prognosis. This suggests DLC1 is a key tumor suppressor gene, particularly in lung, breast, and liver malignancies.

Area of Science:

  • Molecular oncology
  • Cancer genomics
  • Cell signaling

Background:

  • RHO GTPase accelerating proteins (GAPs), including the Deleted in Liver Cancer (DLC) family (DLC1, DLC2, DLC3), are frequently downregulated in tumors.
  • This downregulation can lead to RHO family GTPase activation, promoting tumorigenesis.
  • The specific roles and expression patterns of DLC1, DLC2, and DLC3 in various cancers are not fully elucidated.

Purpose of the Study:

  • To compare the biological activity of DLC1, DLC2, and DLC3 in cultured cells.
  • To analyze mRNA expression patterns of DLC family members in normal and cancer tissues using public datasets.
  • To investigate the association between DLC gene expression, cancer phenotypes, and patient survival outcomes.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) database for mRNA expression levels and copy number variations.
  • Examination of promoter methylation status in specific cancer types.
  • Functional studies in cultured cells to assess Rho-GTP levels and cell migration.
  • Correlation analysis between DLC gene expression and patient survival data.

Main Results:

  • DLC1 expression was predominant in normal lung, breast, and liver tissues, but reduced in lung squamous cell carcinoma (LSC), lung adenocarcinoma (LAD), breast cancer, and hepatocellular carcinoma (HCC).
  • Reduced DLC1 expression was linked to promoter methylation in LSC and LAD, and copy number loss in HCC.
  • Lower DLC1 expression correlated with poorer survival in LAD patients, and combined low DLC1/DLC2 expression indicated the worst prognosis.

Conclusions:

  • DLC1 is the primary DLC family member expressed in several normal tissues and is preferentially downregulated in common cancers originating from these sites.
  • The study highlights DLC1's significant role as a tumor suppressor, with its reduced expression correlating with adverse clinical outcomes.
  • DLC1, and to some extent DLC2, are critical in regulating Rho-GTP activity and cell migration, impacting cancer progression.
Keywords:
DLC genesRhoGAPTCGAbioinformaticstumor suppressor

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