PMID- 35681474
OWN - NLM
STAT- MEDLINE
DCOM- 20220613
LR  - 20220716
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 11
DP  - 2022 May 29
TI  - The Outside-In Journey of Tissue Transglutaminase in Cancer.
LID - 10.3390/cells11111779 [doi]
LID - 1779
AB  - Tissue transglutaminase (TG2) is a member of the transglutaminase family that 
      catalyzes Ca(2+)-dependent protein crosslinks and hydrolyzes guanosine 
      5'-triphosphate (GTP). The conformation and functions of TG2 are regulated by 
      Ca(2+) and GTP levels; the TG2 enzymatically active open conformation is 
      modulated by high Ca(2+) concentrations, while high intracellular GTP promotes 
      the closed conformation, with inhibition of the TG-ase activity. TG2's unique 
      characteristics and its ubiquitous distribution in the intracellular compartment, 
      coupled with its secretion in the extracellular matrix, contribute to modulate 
      the functions of the protein. Its aberrant expression has been observed in 
      several cancer types where it was linked to metastatic progression, resistance to 
      chemotherapy, stemness, and worse clinical outcomes. The N-terminal domain of TG2 
      binds to the 42 kDa gelatin-binding domain of fibronectin with high affinity, 
      facilitating the formation of a complex with beta-integrins, essential for cellular 
      adhesion to the matrix. This mechanism allows TG2 to interact with key matrix 
      proteins and to regulate epithelial to mesenchymal transition and stemness. Here, 
      we highlight the current knowledge on TG2 involvement in cancer, focusing on its 
      roles translating extracellular cues into activation of oncogenic programs. 
      Improved understanding of these mechanisms could lead to new therapeutic 
      strategies targeting this multi-functional protein.
FAU - Sima, Livia Elena
AU  - Sima LE
AUID- ORCID: 0000-0002-3404-4162
AD  - Department of Molecular Cell Biology, Institute of Biochemistry of the Romanian 
      Academy, 060031 Bucharest, Romania.
FAU - Matei, Daniela
AU  - Matei D
AUID- ORCID: 0000-0003-2169-5035
AD  - Department of Obstetrics and Gynecology, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL 60611, USA.
AD  - Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL 60611, USA.
AD  - Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
FAU - Condello, Salvatore
AU  - Condello S
AUID- ORCID: 0000-0003-4979-3681
AD  - Department of Obstetrics and Gynecology, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
AD  - Simon Comprehensive Cancer Center, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20220529
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (TGM2 protein, human)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Epithelial-Mesenchymal Transition
MH  - GTP-Binding Proteins/metabolism
MH  - Guanosine Triphosphate
MH  - Humans
MH  - *Neoplasms/pathology
MH  - *Protein Glutamine gamma Glutamyltransferase 2
MH  - Transglutaminases/metabolism
PMC - PMC9179582
OTO - NOTNLM
OT  - cancer
OT  - cancer stem cells
OT  - extracellular matrix
OT  - fibronectin
OT  - immune cells
OT  - integrin
OT  - therapy
OT  - tissue transglutaminase
OT  - tumor microenvironment
COIS- The authors declare no conflict of interest. The funders had no role in the 
      writing of the manuscript, or in the decision to publish it.
EDAT- 2022/06/11 06:00
MHDA- 2022/06/14 06:00
PMCR- 2022/05/29
CRDT- 2022/06/10 01:08
PHST- 2022/03/29 00:00 [received]
PHST- 2022/05/20 00:00 [revised]
PHST- 2022/05/25 00:00 [accepted]
PHST- 2022/06/10 01:08 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/14 06:00 [medline]
PHST- 2022/05/29 00:00 [pmc-release]
AID - cells11111779 [pii]
AID - cells-11-01779 [pii]
AID - 10.3390/cells11111779 [doi]
PST - epublish
SO  - Cells. 2022 May 29;11(11):1779. doi: 10.3390/cells11111779.