LATS1 tumor suppressor is a novel actin-binding protein and negative regulator of actin polymerization

Grieve, Sandra; Zhou, Zhansong; She, Yi‐Min; Huang, He; Cyr, Terry D.; Xu, Tian; Yang, Xiaolong

doi:10.1038/cr.2011.122

Cited by 42 publications

(43 citation statements)

References 9 publications

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“…In the retina cells with the loss of Mst1, cells endure a excessive proliferation, which can be explained by loss of the ability of Mst1 in inhibiting cell growth and the over expression of CyclinE (Harvey et al, 2003). Related research has suggested that the knockdown of Lats1 in mice can result in ovarian tumor and soft tissue sarcoma (Visser-Grieve et al, 2011). The super-methylation of Lats1 is associated with astrocytoma and mammary cancer (Visser-Grieve et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou¹,

Li²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou¹,

Li²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Another interesting possibility is that mechanosensitive CSK integrity may help sequester proteins on F-actin that can interfere with YAP/TAZ (such as Angiomotin and Lats1/2) to prevent their nuclear translocation and transcriptional activation. Indeed, Lats1 has recently been identified as an actin-depolymerizing factor [125], supporting Hippo-independent regulation of Lats1 in controlling YAP/TAZ via F-actin dynamics and CSK integrity.…”

Section: Harnessing Mechanobiology For Bioengineered 3d Hpsc Culturementioning

confidence: 97%

“…Interestingly, stability of angiomotin binding to F-actin can be regulated by Lats1/2 through phosphorylation of angiomotin, leading to its cytoplasmic accumulation and reduced association with the actin CSK, converging on YAP/TAZ inactivation [123,124]. In addition, Lats1 has recently been identified as an actin binding protein, suggesting its involvement in non-canonical Hippo signaling through sequestration to F-actin [125]. Regulation of YAP/TAZ through angiomotin family proteins and Lats1 in the non-canonical Hippo and Hippo-independent mechanisms has been so far mostly examined in human adult epithelial cells and embryonic kidney cells.…”

Section: Harnessing Mechanobiology For Bioengineered 3d Hpsc Culturementioning

confidence: 99%

On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology

2015

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Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network – with transcriptional coactivators YAP and TAZ at the center stage – that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D.

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“…Several studies noted that the Hippo pathway reduces the F-actin level, which may play important biological roles (Fang and Adler, 2010;Fernández et al, 2011;Visser-Grieve et al 2011;Lucas et al, 2013). In Drosophila wing discs, clones mutant for the Hippo pathway components, such as ex, hpo, sav, mats, and wts, accumulated F-actin at the apical surface.…”

Section: Regulation Of Actin Cytoskeleton By the Hippo Pathwaymentioning

confidence: 99%

“…Several studies indicated that the Hippo pathway regulates actin cytoskeleton in Drosophila (Fang and Adler, 2010;Fernández et al, 2011;Lucas et al, 2013). Others demonstrated the interaction of some of the core Hippo pathway components with F-actin regulators and with β-actin itself (Hirota et al, 2000;Yang et al, 2004;Densham et al, 2009;Rauskolb et al, 2011;Visser-Grieve et al, 2011). Although the biological signifi cance of this reverse regulation is not fully understood, it may play an important role in establishing a feedback loop.…”

Section: Introductionmentioning

confidence: 99%

Mutual regulation between Hippo signaling and actin cytoskeleton

Matsui

Lai

2013

Protein Cell

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Hippo signaling plays a crucial role in growth control and tumor suppression by regulating cell proliferation, apoptosis, and differentiation. How Hippo signaling is regulated has been under extensive investigation. Over the past three years, an increasing amount of data have supported a model of actin cytoskeleton blocking Hippo signaling activity to allow nuclear accumulation of a downstream effector, Yki/Yap/Taz. On the other hand, Hippo signaling negatively regulates actin cytoskeleton organization. This review p rovides insight on the mutual regulatory mechanisms between Hippo signaling and actin cytoskeleton for a tight control of cell behaviors during animal development, and points out outstanding questions for further investigations.

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LATS1 tumor suppressor is a novel actin-binding protein and negative regulator of actin polymerization

Cited by 42 publications

References 9 publications

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology

Mutual regulation between Hippo signaling and actin cytoskeleton

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