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Dissecting the Functional Role of the TRIM8 Protein on Cancer Pathogenesis.

Jessica Elisabetta Esposito1, Vincenzo De Iuliis2, Francesco Avolio1

  • 1Center of Advanced Studies and Technology, Department of Innovative Technology in Medicine and Dentistry, University of Chieti, 66100 Chieti, Italy.

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Summary

The TRIM8 protein plays a dual role in cancer, acting as either an oncogene or tumor suppressor. Its function impacts breast cancer and glioma, influencing proliferation and patient survival through various signaling pathways.

Keywords:
JAK-STATNF-kBTRIM proteinsTRIM8cancerp53

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • The Tripartite Motif (TRIM) and Really Interesting New Gene (RING) - B-Box - Coiled-Coil (RBCC) protein family encompasses over 80 members, many functioning as E3 ligases.
  • These proteins are critical in ubiquitination, SUMOylation, and ISG15ylation, impacting oncogenesis and cellular immunity.

Purpose of the Study:

  • To review the multifaceted roles of TRIM8 in various tumor pathologies.
  • To elucidate the dual function of TRIM8 as an oncogene or tumor suppressor in cancer development.

Main Methods:

  • Literature review summarizing existing research on TRIM8.
  • Analysis of TRIM8's involvement in key signaling pathways such as estrogen signaling, p53, NF-kB, and JAK-STAT (including STAT3).

Main Results:

  • TRIM8 inhibits breast cancer proliferation by regulating estrogen signaling.
  • Downregulation of TRIM8 in glioma correlates with increased cell proliferation and reduced patient survival.
  • TRIM8 interacts with critical pathways including p53, Nuclear Factor kappa light-chain-enhancer of activated B cells (NF-kB), and Signal Transducer and Activator of Transcription 3 (STAT3) in the JAK-STAT pathway.

Conclusions:

  • The interplay between different signaling pathways highlights TRIM8's complex role in cancer.
  • TRIM8's function as an oncogene or tumor suppressor is context-dependent, offering potential therapeutic targets.