Down-regulation of tensin2 enhances tumorigenicity and is associated with a variety of cancers

Abstract

Tensin family members, including tensin2 (TNS2), are present as major components of the focal adhesions. The N-terminal end of TNS2 contains a C1 region (protein kinase C conserved region 1) that is not found in other tensin members. Three isoforms of TNS2 have been identified with previous reports describing the shortest V3 isoform as lacking the C1 region. Although TNS2 is known to regulate cell proliferation and migration, its role in tumorigenicity is controversial. By gain-of-function overexpression approaches, results supporting either promotion or reduction of cancer cell tumorigenicity were reported. Here we report that the complete V3 isoform also contains the C1 region and describe the expression patterns of the three human TNS2 isoforms. By loss-of-function approaches, we show that silencing of TNS2 up-regulates the activities of Akt, Mek, and IRS1, and increases tumorigenicities in A549 and Hela cells. Using public database analyses we found that TNS2 is down-regulated in head and neck, esophageal, breast, lung, liver, and colon cancer. In addition, patients with low TNS2 expression showed poor relapse-free survival rates for breast and lung cancers. These results strongly suggest a role of tensin2 in suppressing cell transformation and reduction of tumorigenicity.

SIRT2 Promotes the Migration and Invasion of Gastric Cancer through RAS/ERK/JNK/MMP-9 Pathway by Increasing PEPCK1-Related Metabolism

“…Accordingly, we queried tissue microarrays from SHANGHAI OUTDO BIOTECH, which contains 84 gastric cancer samples, and found that SIRT2 was significantly increased in tumor tissues compared to adjacent tissues ( Figure 1 , A - C ). We queried the Kaplan-Meier plotter ( http://kmplot.com/analysis ) database [17] , [18] , which contains clinically annotated genomic data from gastric cancer samples, and found that high Sirt2 mRNA expression was associated with poor progression-free survival and overall survival (log-rank test) ( Figure 1 , D & E ). We further assessed the expression of SIRT2 in GC cell lines (AGS, HGC-27, MGC-803 and MKN-45) and normal gastric epithelial cells (GES-1) and found that the expression level of SIRT2 in GC cells was significantly higher than that of GES-1 cells ( Figure 1 F ).…”

Deletion of the Tensin2 SH2-PTB domain, but not the loss of its PTPase activity, induces podocyte injury in FVB/N mouse strain

“…Tensin family members are known as focal adhesion proteins, and are known to be localized to focal adhesion in at least in some cell types [8]. in a podocyte cell line, the transfected full-length TNS2 displayed a peripheral dotted distribution pattern typical of a focal adhesion protein as in other cell types [2,9,14,31]. On the other hand, the distribution of the TNS2 ∆SH2-PTB in the podocyte cell line was distinct from that of the full-length TNS2; i.e., a focal adhesion protein.…”

Perturbed functional networks in Alzheimer’s Disease reveal opposing roles for TGIF and EGR3

“…Tensin 2 (TNS2) is a focal adhesion protein that regulates signaling pathways for cell shape and motility by bridging cytoskeleton and intracellular projections of transmembrane receptors. By acting as a protein tyrosine phosphatase, TNS2 dephosphorylates IRS1 reducing its activation for binding to signaling molecules and reduces Akt signaling via a negative feedback loop 39 . Centrosomal protein 57 (CEP57) mediates the mitogenic activity of fibroblast growth factor 2 (FGF2) which shows enhanced binding to senile plaques and neurofibrillary tangles and stimulates downstream signaling pathways (MAPK/ERK, PLC, Akt) 22,47,75 .…”