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Caspase-8 and Tyrosine Kinases: A Dangerous Liaison in Cancer

Claudia Contadini1,2, Alessandra Ferri3, Claudia Cirotti1,2

  • 1Laboratory of Cell Signaling, IRCCS-Fondazione Santa Lucia, 00179 Rome, Italy.

Cancers
|July 14, 2023
PubMed

Insights

Caspase-8, crucial for apoptosis, has dual roles in cancer. While often silenced, it can promote tumor growth and therapy resistance through non-apoptotic functions, particularly when interacting with tyrosine kinases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Caspase-8 is an initiator caspase vital for the extrinsic apoptotic pathway.
  • Apoptosis evasion is a cancer hallmark; Caspase-8 silencing occurs in some tumors.
  • Conversely, elevated Caspase-8 expression and non-apoptotic roles in cancer progression and therapy resistance are increasingly reported.

Purpose of the Study:

  • To review and discuss the multifaceted role of Caspase-8 in cancer.
  • To explore the interplay between Caspase-8 and tyrosine kinases in oncogenesis.
  • To understand how cancer cells hijack Caspase-8 activity.

Main Methods:

  • Literature review and synthesis of existing research findings.
  • Analysis of genomic, transcriptomic, and proteomic data on tyrosine kinase activation in tumors.
  • Discussion of signaling pathways involved in Caspase-8 rewiring.

Main Results:

  • Caspase-8 exhibits context-dependent roles in cancer, acting as both a tumor suppressor and promoter.
  • Non-canonical functions of Caspase-8 contribute to cancer progression and treatment resistance.
  • Tyrosine kinases, frequently activated in tumors, are implicated in aberrant Caspase-8 signaling.

Conclusions:

  • Cancer cells can reprogram Caspase-8 function, leading to pro-tumorigenic activities.
  • The interaction between Caspase-8 and activated tyrosine kinases is a critical aspect of cancer biology.
  • Targeting Caspase-8 and associated tyrosine kinase pathways may offer novel therapeutic strategies.
Keywords:
Caspase-8NF-kB signalingcancercell cycletyrosine kinase

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