The four-and-a-half-LIM protein 2 (FHL2) is overexpressed in gliomas and associated with oncogenic activities

Glia. 2008 Sep;56(12):1328-38. doi: 10.1002/glia.20701.


Four-and-a-half-LIM protein 2 (FHL2) is a member of FHL protein family, which plays a crucial role in regulating gene expression, cell survival, and migration. Although its function in oncogenesis appears to be tumor type-specific, its roles in glioma formation and development are yet to be elucidated. In the present study, we demonstrated that the mRNA level of FHL2 was elevated in both low- and high-grade glioma samples. Overexpression of FHL2 stimulated the proliferation, anchorage-independent growth, and migration of human glioblastoma cells. Conversely, FHL2 knockdown by short hairpin RNA (shRNA-FHL2) inhibited glioblastoma cell proliferation and migration. Overexpression of FHL2 increased the tumorigenicity of glioblastoma cells in nude mice and decreased the mRNA levels of p53 and its downstream proapoptotic genes, including p21, Bcl2-associated protein X (Bax), and p53-upregulated modulator of apoptosis. It also enhanced the promoter activities of activator protein-1 (AP-1), human telomerase reverse transcriptase, and survivin genes. Together, these results provide the first evidence that FHL2 contributes to glioma carcinogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Enzyme Activation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioma / genetics*
  • Glioma / metabolism
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • LIM-Homeodomain Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / genetics*
  • Oncogenes / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation / genetics


  • FHL2 protein, human
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Muscle Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Transcription Factors
  • Tumor Suppressor Protein p53