PMID- 17372902
OWN - NLM
STAT- MEDLINE
DCOM- 20070816
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 121
IP  - 3
DP  - 2007 Aug 1
TI  - Cytoplasmic accumulation of connexin32 protein enhances motility and metastatic 
      ability of human hepatoma cells in vitro and in vivo.
PG  - 536-46
AB  - Connexins have long been believed to suppress tumour development during 
      carcinogenesis by exerting gap junctional intercellular communication (GJIC). 
      Although GJIC is abrogated in hepatocellular carcinoma (HCC), connexin32 (Cx32) 
      protein tends to remain expressed in cytoplasm, but not in cell-cell contact 
      areas; thus, it is incapable of forming gap junctions. Hypothesising that 
      cytoplasmic Cx32 protein that has accumulated in HCC should have its proper 
      functions, which are independent of GJIC, we established an inducible expression 
      system of Cx32 in human HuH7 HCC cells, which were unable to support the 
      formation of Cx32-mediated gap junctions, so that Cx32 protein could be 
      overexpressed by doxycycline (Dox) withdrawal. Although the established clone 
      HuH7 Tet-off Cx32 cells exhibited a 4-fold increase in Cx32 expression after Dox 
      withdrawal, none of them were dye-coupled, and Cx32 protein was retained in the 
      Golgi apparatus. However, the proliferation rate of the HuH7 Tet-off Cx32 cells 
      was significantly higher in the Dox-free medium than in the Dox-supplemented one. 
      Transwell assays also revealed that Dox withdrawal enhanced serum-stimulated 
      motility and invasiveness into Matrigel of the HuH7 Tet-off Cx32 cells. 
      Furthermore, when HuH7 Tet-off Cx32 cells were xenografted into the liver of SCID 
      mice, only the mice to which no Dox was administered developed metastatic 
      lesions, indicating that overexpression of cytoplasmic Cx32 protein induced 
      metastasis of HuH7 cells. Our results suggest that, while Cx32-mediated GJIC 
      suppresses the development of HCCs, cytoplasmic Cx32 protein exerts effects 
      favourable for HCC progression, such as invasion and metastasis, once the cells 
      have acquired a malignant phenotype.
CI  - Copyright (c) 2007 Wiley-Liss, Inc.
FAU - Li, Qingchang
AU  - Li Q
AD  - Department of Pathology and Immunology, Akita University School of Medicine, 
      1-1-1 Hondo, Akita, Japan.
FAU - Omori, Yasufumi
AU  - Omori Y
FAU - Nishikawa, Yuji
AU  - Nishikawa Y
FAU - Yoshioka, Toshiaki
AU  - Yoshioka T
FAU - Yamamoto, Youhei
AU  - Yamamoto Y
FAU - Enomoto, Katsuhiko
AU  - Enomoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*metabolism/*pathology
MH  - Cell Adhesion
MH  - Cell Communication
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cytoplasm/*metabolism
MH  - Doxycycline/metabolism
MH  - Gap Junctions/metabolism
MH  - Humans
MH  - Liver Neoplasms/*metabolism/*pathology
MH  - Liver Neoplasms, Experimental/metabolism/pathology
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Tumor Cells, Cultured
EDAT- 2007/03/21 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/03/21 09:00
PHST- 2007/03/21 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/03/21 09:00 [entrez]
AID - 10.1002/ijc.22696 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Aug 1;121(3):536-46. doi: 10.1002/ijc.22696.