PMID- 17662645
OWN - NLM
STAT- MEDLINE
DCOM- 20080103
LR  - 20220321
IS  - 1368-7646 (Print)
IS  - 1368-7646 (Linking)
VI  - 10
IP  - 4-5
DP  - 2007 Aug-Oct
TI  - Tissue transglutaminase-mediated chemoresistance in cancer cells.
PG  - 144-51
AB  - Drug resistance and metastasis are major impediments for the successful treatment 
      of cancer. A common feature among drug resistant and metastatic tumor cells is 
      that they exhibit profound resistance to apoptosis. This property enables cancer 
      cells not only to grow and survive in stressful environments (metastasis) but 
      also to display resistance against many anticancer agents. Therefore, 
      perturbation of the intrinsic apoptotic pathways of cancer cells will affect 
      their ability to respond to chemotherapy and to metastasize and survive in 
      distant sites. Recent studies have demonstrated that cancer cells and cancer cell 
      lines selected for resistance against chemotherapeutic drugs or isolated from 
      metastatic sites, express elevated levels of the multifunctional protein, tissue 
      transglutaminase (TG2). TG2 is the most diverse and ubiquitous member of the 
      transglutaminase family of proteins that is implicated to play a role in 
      apoptosis, wound healing, cell migration, cell attachment, cell growth, 
      angiogenesis, and matrix assembly. TG2 can associate with certain beta members of 
      the integrin family of proteins (beta1, beta3, beta4, and beta5) and promote 
      stable interaction between cells and the extracellular matrix (ECM), resulting in 
      increased cell survival, cell migration, and invasion. Additionally, TG2 forms a 
      ternary complex with IkappaB/p65:p50 and results in constitutive activation of 
      the nuclear transcription factor-kappaB (NF-kappaB). Moreover, TG2 expression in 
      cancer cells leads to constitutive activation of the focal adhesion kinase (FAK) 
      and its downstream PI3K/Akt survival pathway. Importantly, the inhibition of 
      endogenous TG2 by small interfering RNA (siRNA) resulted in the reversal of drug 
      resistance and the invasive phenotype. Conversely, ectopic expression of TG2 
      promoted cell survival, cell motility and invasive functions of cancer cells. 
      This review discusses the current thinking and implications of increased TG2 
      expression in development of drug resistance and metastasis by cancer cells.
FAU - Verma, Amit
AU  - Verma A
AD  - Department of Experimental Therapeutics, Unit 362, The University of Texas M. D. 
      Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, United 
      States.
FAU - Mehta, Kapil
AU  - Mehta K
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20070727
PL  - Scotland
TA  - Drug Resist Updat
JT  - Drug resistance updates : reviews and commentaries in antimicrobial and 
      anticancer chemotherapy
JID - 9815369
RN  - 0 (Antineoplastic Agents)
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  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Apoptosis/drug effects
MH  - *Drug Resistance, Neoplasm
MH  - GTP-Binding Proteins/*antagonists & inhibitors/genetics/metabolism
MH  - Humans
MH  - Models, Biological
MH  - Neoplasms/*drug therapy/enzymology/genetics
MH  - Protein Glutamine gamma Glutamyltransferase 2
MH  - Transglutaminases/*antagonists & inhibitors/genetics/metabolism
RF  - 77
EDAT- 2007/07/31 09:00
MHDA- 2008/01/04 09:00
CRDT- 2007/07/31 09:00
PHST- 2007/05/16 00:00 [received]
PHST- 2007/06/08 00:00 [revised]
PHST- 2007/06/11 00:00 [accepted]
PHST- 2007/07/31 09:00 [pubmed]
PHST- 2008/01/04 09:00 [medline]
PHST- 2007/07/31 09:00 [entrez]
AID - S1368-7646(07)00042-8 [pii]
AID - 10.1016/j.drup.2007.06.002 [doi]
PST - ppublish
SO  - Drug Resist Updat. 2007 Aug-Oct;10(4-5):144-51. doi: 10.1016/j.drup.2007.06.002. 
      Epub 2007 Jul 27.