Advanced

Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.

Martuszewska, Danuta LU ; Ljungberg, Börje; Johansson, Martin LU ; Landberg, Göran LU ; Oslakovic, Cecilia LU ; Dahlbäck, Björn LU and Hafizi, Sassan LU (2009) In PLoS One 4(2).
Abstract
BACKGROUND: The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. PRINCIPAL FINDINGS: Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated... (More)
BACKGROUND: The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. PRINCIPAL FINDINGS: Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001). Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration. CONCLUSIONS: Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary tumors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS One
volume
4
issue
2
publisher
Public Library of Science
external identifiers
  • WOS:000265483500006
  • PMID:19194507
  • Scopus:84887212457
ISSN
1932-6203
DOI
10.1371/journal.pone.0004350
language
English
LU publication?
yes
id
e6b87728-663c-49c9-8e9a-74862191ffc1 (old id 1302879)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19194507?dopt=Abstract
date added to LUP
2009-03-04 14:57:59
date last changed
2017-01-01 07:46:29
@article{e6b87728-663c-49c9-8e9a-74862191ffc1,
  abstract     = {BACKGROUND: The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. PRINCIPAL FINDINGS: Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P&lt;0.001). Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration. CONCLUSIONS: Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary tumors.},
  articleno    = {e4350},
  author       = {Martuszewska, Danuta and Ljungberg, Börje and Johansson, Martin and Landberg, Göran and Oslakovic, Cecilia and Dahlbäck, Björn and Hafizi, Sassan},
  issn         = {1932-6203},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS One},
  title        = {Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0004350},
  volume       = {4},
  year         = {2009},
}