Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression

Wakoh, Takeshi; Uekawa, Natsuko; Terauchi, Kunihiko; Sugimoto, Masataka; Ishigami, Akihito; Shimada, Junichi; Maruyama, Mitsuo

doi:10.1016/j.bbrc.2009.01.171

Cited by 17 publications

(15 citation statements)

References 30 publications

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“…Similarly, loss of Abi3bp RNA expression has been reported in both lung cancer cell-lines and lung tumor specimens [12]. Abi3bp has been reported to have both a positive and negative role in senescence [13, 14]. In this study we show that Abi3bp plays an important role in MSC biology by acting as a “check and balance” in many MSC processes including proliferation, differentiation, adhesion, morphology and transformation.…”

Section: Introductionsupporting

confidence: 78%

Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology

et al. 2013

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Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs overexpressing AKT1 (Akt-MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp towards MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin-mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress-fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt-MSC proliferation, promoting S-phase entry via cyclin-d1, ERK1/2 and Src. Upon Abi3bp binding to integrin-β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs.

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Section: Introductionsupporting

confidence: 78%

Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology

et al. 2013

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“…In addition, p21 also contributes to drug-induced apoptosis in cancer cells (31,32). Expression of p21 in cancer cells may be dependent or independent of p53 (33)(34)(35)(36). The present study showed that LLFE treatment resulted in cell senescence accompanied by upregulation of p21 and downregulation of RB phosphorylation, suggesting that p21/RB may contribute to LLFE-induced cell senescence.…”

Section: Discussionmentioning

confidence: 51%

Ligustrum lucidum Ait. fruit extract induces apoptosis and cell senescence in human hepatocellular carcinoma cells through upregulation of p21

Deng

et al. 2014

Oncology Reports

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Nü-zhen-zi, the fruit of Ligustrum lucidum Ait., is one of the most frequently used liver Yin tonifying Chinese herbs for the treatment of liver cancer. However, the effect of Ligustrum lucidum fruit on hepatocarcinoma cells remains unknown. In the present study, we evaluated the effects of a Ligustrum lucidum fruit extract (LLFE) on human hepatocellular carcinoma Bel-7402 cells. The results showed that LLFE inhibited the proliferation of the Bel-7402 cells in a dose- and time-dependent manner. LLFE induced apoptosis in Bel-7402 cells accompanied by activation of caspase-3, -8 and -9. LLFE-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. LLFE treatment also caused a large and flat morphologic cellular change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in the Bel-7402 cells, accompanied by upregulation of p21 and downregulation of RB phosphorylation. Specific knockdown of p21 expression by RNA interference partially abrogated LLFE-induced apoptosis, and significantly abrogated LLFE-induced cell senescence. These observations suggest that Nü-zhen-zi is a potential anticancer herb and support the traditional use of Nü-zhen-zi for hepatocarcinoma treatment.

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“…This protein was approximately 19-fold higher in the CM of NF1 Schwann cells relative to normal Schwann cells. TARSH was recently described to play a role in cell senescence via the p53 pathway [17] but also play a major role in reducing cell dendritic complexity of neural cells [18]. This later function might be relevant to the differentiation of neural and Schwann cells in the context of neurofibroma progression.…”

Section: Resultsmentioning

confidence: 99%

Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

Chen

Seol²,

Brown³

et al. 2012

IJMS

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To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. The proteins with increased levels included proteins involved in cell growth, angiogenesis and complement pathway while proteins with decreased levels included those involved in cell adhesion, plasminogen pathway and extracellular matrix remodeling. Retinoic acid receptor responder protein-1 (RARRES1), previously described as an integral membrane tumor suppressor, was found exclusively secreted by NF1 Schwann cells but not by normal Schwann cells. All-trans retinoic acid modulated secretion of RARRES1 in a dose dependent manner. This study shows altered secretion of key proteins in NF1 derived Schwann cells. The potential implication of these proteins in neurofibroma biology is discussed.

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Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression

Cited by 17 publications

References 30 publications

Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology

Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology

Ligustrum lucidum Ait. fruit extract induces apoptosis and cell senescence in human hepatocellular carcinoma cells through upregulation of p21

Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

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