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Tissue transglutaminase: a new target to reverse cancer drug resistance

Alfredo Budillon1, Carmine Carbone, Elena Di Gennaro

  • 1Experimental Pharmacology Unit, Department of Research, Istituto Nazionale Tumori, National Cancer Institute G. Pascale, Via M. Semmola, 80131 Naples, Italy. a.budillon@istitutotumori.na.it

Amino Acids
|December 2, 2011
PubMed

Insights

Tissue transglutaminase (TG2) plays a complex role in cancer drug resistance and apoptosis evasion. Inhibiting TG2 may reverse resistance and sensitize cancer cells to treatments, offering new therapeutic avenues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer resistance mechanisms limit anti-cancer treatment efficacy.
  • Tissue transglutaminase (TG2) is implicated in tumor cell drug resistance and apoptosis evasion.
  • TG2 exhibits both pro-survival and anti-apoptotic roles in malignant cells, with increased expression linked to poor prognosis, metastasis, and drug resistance.

Purpose of the Study:

  • To explore the multifaceted role of tissue transglutaminase (TG2) in cancer drug resistance.
  • To investigate TG2's mechanisms in mediating resistance, including survival pathways, apoptosis inhibition, ECM formation, EMT, and autophagy.
  • To highlight the therapeutic potential of TG2 inhibition for overcoming cancer drug resistance.

Main Methods:

  • Review of existing literature on TG2 expression and function in various cancers.
  • Analysis of studies investigating TG2's involvement in drug resistance and apoptosis.
  • Examination of preclinical data on TG2 inhibitors and their efficacy.

Main Results:

  • TG2 expression is frequently elevated in tumors and correlates with advanced disease and drug resistance.
  • TG2 mediates resistance by activating survival pathways, inhibiting apoptosis, and influencing ECM, EMT, and autophagy.
  • TG2 knockdown or inhibition can reverse drug resistance and enhance apoptosis in cancer cells.

Conclusions:

  • TG2 is a significant contributor to cancer drug resistance through diverse mechanisms.
  • Inhibiting TG2 activity or expression presents a promising strategy to re-sensitize cancer cells to therapies.
  • Further translational research on TG2's role in cancer is crucial for developing novel therapeutic approaches.

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