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TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

Yuta Yamada1, Naoki Kimura1,2, Ken-Ichi Takayama2

  • 1Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Cancer Science
|December 29, 2019
PubMed

Insights

High expression of TRIM44 correlates with poor prognosis in renal cell carcinoma (RCC). This study found TRIM44 promotes cancer cell proliferation and migration by regulating FRK in RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The oncogenic roles of TRIM44 are established in several cancers.
  • Its expression and function in renal cell carcinoma (RCC) remain largely uncharacterized.

Purpose of the Study:

  • To investigate the clinical significance and biological function of TRIM44 in RCC.
  • To identify potential molecular mechanisms underlying TRIM44's role in RCC progression.

Main Methods:

  • Analysis of TRIM44 expression in RCC patient data, correlating it with clinical parameters and survival outcomes.
  • In vitro gain-of-function and loss-of-function studies using TRIM44 and siTRIM44 in RCC cell lines (Caki1, 769P).
  • Integrated microarray analysis and database exploration (Oncomine) to identify TRIM44 target genes, followed by functional validation.

Main Results:

  • TRIM44 overexpression is significantly associated with advanced M stage, clear cell histology, and lymphatic invasion in RCC.
  • TRIM44 overexpression predicts poor cancer-specific survival in RCC patients.
  • TRIM44 promotes RCC cell proliferation and migration; FRK is identified as a key downstream target gene, whose downregulation in RCC is reversed by TRIM44, and its knockdown inhibits proliferation.

Conclusions:

  • TRIM44 is a significant prognostic biomarker in RCC, associated with aggressive clinicopathological features and poor survival.
  • TRIM44 promotes RCC progression, at least in part, by upregulating FRK expression, highlighting a potential therapeutic target.
Keywords:
FRKTRIMimmunohistochemistrymicroarrayrenal cell carcinoma

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