The Role of Transglutaminase 2 in Cancer: An Update

Author:

Zaltron Elisabetta1,Vianello Federica1,Ruzza Alessia1ORCID,Palazzo Alberta1,Brillo Valentina1,Celotti Ilaria1,Scavezzon Matteo1,Rossin Federica2,Leanza Luigi1ORCID,Severin Filippo1ORCID

Affiliation:

1. Department of Biology, University of Padua, 35131 Padua, Italy

2. Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy

Abstract

Transglutaminase type 2 (TG2) is the most ubiquitously expressed and well characterized member of the transglutaminase family. It is a ubiquitous multifunctional enzyme implicated in the regulation of several cellular pathways that support the survival, death, and general homeostasis of eukaryotic cells. Due to its multiple localizations both inside and outside the cell, TG2 participates in the regulation of many crucial intracellular signaling cascades in a tissue- and cell-specific manner, making this enzyme an important player in disease development and progression. Moreover, TG2 is capable of modulating the tumor microenvironment, a process of dynamic tissue remodeling and biomechanical events, resulting in changes which influence tumor initiation, growth, and metastasis. Even if generally related to the Ca2+-dependent post-translational modification of proteins, a number of different biological functions have been ascribed to TG2, like those of a peptide isomerase, protein kinase, guanine nucleotide binder, and cytosolic–nuclear translocator. With respect to cancer, TG2′s role is controversial and highly debated; it has been described both as an anti- and pro-apoptotic factor and is linked to all the processes of tumorigenesis. However, numerous pieces of evidence support a tissue-specific role of TG2 so that it can assume both oncogenic and tumor-suppressive roles.

Funder

MFAG 2019

MFAG2022

University of Padova Programme

PRID 2017

Italian Ministry of University and Education

National Center for Gene Therapy and Drugs based on RNA Technology

Publisher

MDPI AG

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