Molecular characterization of human tensin

Chen, Huaiyang; ISHII, Akiko; Wong, Wai-Keung; Chen, Lan Bo; Lo, Su Hao

doi:10.1042/0264-6021:3510403

Cited by 51 publications

(65 citation statements)

References 14 publications

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“…Tensin family members have been shown to be downregulated in various cancer cells 14,19 ; however, variant 3, the smallest isoform of tensin2 and lacking the characteristic C1 domain in the N terminal, was capable of promoting cell migration. 16 In the present study, we found that variant 3 was overexpressed in human HCC tissue compared with the corresponding nontumorous liver tissue (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma†

Yam

Chan

et al. 2006

Hepatology

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Tensins are a new family of proteins that act as an important link among extracellular matrix, actin cytoskeleton, and signal transduction and have been implicated in human cancers. Tensin2 was initially identified in a search for new tensin family members that share extensive sequence homology with tensin1. Tensin2 was highly expressed in liver tissues. A recent study reported that one of the splicing variants of tensin2, variant 3, promotes cell migration. In the present study, we aimed to elucidate the role of H epatocellular carcinoma (HCC) is one of the major malignancies worldwide and the second most common fatal cancer in Asia and Hong Kong. The molecular mechanisms underlying the development, invasion, and metastasis of HCC are areas of active research. A better understanding of these areas may lead to the development of more effective prognostic markers and potential therapies for HCC. Adhesion proteins including intracellular adhesion molecule 1, 1 E-cadherin, 2 CD44 variants, 3 and extracellular matrix protein, laminin-5 4 have been reported to be biomarkers for an invasive and metastatic phenotype of HCC. Proteinases responsible for the degradation of extracellular matrix, for instance, matrix metalloproteinase, 5 urokinase-type plasminogen activator, 6 uPA receptor, and uPA inhibitor, 7 are also important factors involved in the invasiveness and metastasis of HCC. Angiogenesis regulators critical to HCC metastasis has drawn a lot of attention in recent years. Vascular endothelial growth factor, 8 angiopoietin, 9 basic fibroblast growth factor, 10 platelet-derived endothelial cell growth factor, 11 and thrombospondin 12 have been reported to be angiogenic factors crucial to HCC angiogenesis.Tensin is a new family of focal adhesion proteins that act as an important link among extracellular matrix (ECM), actin cytoskeleton, and signal transduction. 13 Recent studies have revealed that tensin proteins are also implicated in human cancers. Tensin1 is the most wellcharacterized member and best known for its activity in organizing the actin cytoskeleton and mediating signal transduction. 13 Expression of human tensin1 was shown to be down-regulated in prostate and breast cancer cell From the

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Section: Discussionmentioning

confidence: 99%

“…13 Expression of human tensin1 was shown to be down-regulated in prostate and breast cancer cell lines. 14 Induction of tensin1 by cancer chemopreventive agent contributes to the anti-invasive activity of cancer cells. 15 Very recently, other structurally related tensin family members have been identified.…”

mentioning

confidence: 99%

Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma†

Yam

Chan

et al. 2006

Hepatology

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“…Tensin2 is a member of tensin family, a focal-adhesion-molecule that stabilizes F-actin by binding to -integrin [4], as did -actinin4 (ACTN4) [21]. Of interest, a loss of tensin2 acts as a switch to trigger cell migration [27].…”

Section: Discussionmentioning

confidence: 99%

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

Kato

Mizuno-Horikawa

Mizuno

2011

The Journal of Veterinary Medical Science

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ABSTRACT. Podocytes have a peculiar structure constituting slit diaphragm (SD) and foot process (FP), and play essential roles in the glomerular filtration barrier. There is now ample evidence that SD-and FP-associated molecules, such as podocin and CD2-associated protein (CD2AP), are down-regulated during albuminuria of chronic kidney disease. However, it is still unclear whether these molecules are altered during acute renal failure (ARF) with albuminuria. Using lipopolysaccharide (LPS)-treated mice as a model of septic ARF, we provide evidence that the expression of SD-and FP-associated molecules becomes faint, along with albuminuria. In the LPS-treated mice, urinary albumin levels gradually increased, associated with the elevation of blood urea nitrogen levels, indicating the successful induction of albuminuria during septic ARF. In this pathological process, glomerular podocin expression became faint, especially at 36 hr post-LPS challenge (i.e., a peak of albuminuria). Likewise, LPS treatment led to a significant decrease in CD2AP, an anchorage between podocin and F-actin. With regard to this, tensin2 is a novel molecule that stabilizes F-actin extension. Interestingly, glomerular tensin2 expression levels were also decreased during the albuminuric phase, associated with losses of glomerular F-actin and synaptopodin under septic states. As a result, there were some lesions of podocytic FP effacement, as shown by electron microscopy. Based on these data, we emphasize the importance of concomitant decreases in podocin, CD2AP and tensin2 during septic ARF-associated proteinuria.

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“…8A) (5, 19 -22). PTEN is a homolog of tensin (23,24). Since the amino terminus of tensin interacts with actin and within this region tensin shares sequence homology with PTEN, PTEN is a putative actin cytoskeleton-associated molecule.…”

Section: Inhibition Of Akt Activity Restores Sensitivity Of Pten Nullmentioning

confidence: 99%

PTEN Regulates Fibroblast Elimination during Collagen Matrix Contraction

Nho

Xia

Diebold

et al. 2006

Journal of Biological Chemistry

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During tissue repair, excess fibroblasts are eliminated by apoptosis. This physiologic process limits fibrosis and restores normal anatomic patterns. Replicating physiologic apoptosis associated with tissue repair, fibroblasts incorporated into type I collagen matrices undergo apoptosis in response to collagen matrix contraction. In this in vitro model of wound repair, fibroblasts first attach to collagen via ␣2␤1 integrin. This provides a survival signal via activation of the phosphatidylinositol 3-kinase/Akt signal pathway. However, during subsequent collagen matrix contraction, the level of phosphorylated Akt progressively declines, triggering apoptosis. The mechanism underlying the fall in phosphorylated Akt is incompletely understood. Here we show that PTEN phosphatase becomes activated during collagen matrix contraction and is responsible for antagonizing phosphatidylinositol 3-kinase activity and promoting a decline in phosphorylated Akt and fibroblast apoptosis in response to collagen contraction. PTEN null fibroblasts displayed enhanced levels of phosphorylated Akt and were resistant to collagen matrix contraction-induced apoptosis. Reconstitution of PTEN in PTEN null cells conferred susceptibility to apoptosis in response to contraction of collagen matrices. Consistent with this, knockdown of PTEN in PTEN ؉/؉ embryonic fibroblasts by small interfering RNA augmented Akt activity and suppressed apoptosis in contractile collagen matrices. Furthermore, inhibition of Akt activity restored the sensitivity of PTEN null cells to collagen contraction-induced apoptosis, indicating that the mechanism by which PTEN alters fibroblast viability is through modulation of phosphorylated Akt levels. Our work suggests that collagen matrix contraction activates PTEN by a mechanism involving cytoskeletal disassembly. Our studies indicate a key role for PTEN in regulating fibroblast viability during tissue repair.Fibroblasts play an essential role in tissue repair. In response to injury, interstitial fibroblasts differentiate into myofibroblasts (1). Myofibroblasts synthesize and deposit type I collagen into the wound provisional matrix (2). They subsequently contract the type I collagen matrix, facilitating wound closure (3, 4).Following contraction of the type I collagen matrix, myofibroblasts are eliminated by apoptosis, reducing wound cellularity (3). The precise molecular mechanisms governing removal of fibroblasts during tissue repair are unclear.Using fibroblasts cultured in three-dimensional contractile type I collagen matrices as a model of wound/tissue repair, the molecular signals regulating fibroblast viability during collagen contraction have begun to be elucidated. When fibroblasts are incorporated into the type I collagen matrix, they utilize ␣2␤1 integrin to attach and spread (5). This results in phosphorylation of serine 473 of Akt. Activation of Akt provides a survival signal that is mediated through phosphatidylinositol 3-kinase (PI3K) 3 (5-12). However, upon collagen matrix contraction, this integrin sur...

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Molecular characterization of human tensin

Cited by 51 publications

References 14 publications

Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma†

Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma†

Decreases in Podocin, CD2-Associated Protein (CD2AP) and Tensin2 May Be Involved in Albuminuria during Septic Acute Renal Failure

PTEN Regulates Fibroblast Elimination during Collagen Matrix Contraction

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