scholarly journals Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

10.3791/58416 ◽  
2018 ◽  
Author(s):  
Taha Azad ◽  
Kazem Nouri ◽  
Helena J. Janse van Rensburg ◽  
Yawei Hao ◽  
Xiaolong Yang
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Large Tumor ◽  
Pathway Activity ◽  
Hippo Signaling Pathway ◽  
Large Tumor Suppressor

scholarly journals Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1

2018 ◽  
Vol 10 (6) ◽  
pp. 549-558 ◽  
Author(s):  
Lauren Rusnak ◽  
Cong Tang ◽  
Qi Qi ◽  
Xiulei Mo ◽  
Haian Fu
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Cellular Response ◽  
Regulatory System ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Hippo Signaling ◽  
Large Tumor ◽  
Large Tumor Suppressor

Abstract Apoptosis signal-regulating kinase 1 (ASK1) is an important mediator of the cell stress response pathways. Because of its central role in regulating cell death, the activity of ASK1 is tightly regulated by protein–protein interactions and post-translational modifications. Deregulation of ASK1 activity has been linked to human diseases, such as neurological disorders and cancer. Here we describe the identification and characterization of large tumor suppressor 2 (LATS2) as a novel binding partner for ASK1. LATS2 is a core kinase in the Hippo signaling pathway and is commonly downregulated in cancer. We found that LATS2 interacts with ASK1 and increases ASK1-mediated signaling to promote apoptosis and activate the JNK mitogen-activated protein kinase (MAPK). This change in MAPK signaling is dependent on the catalytic activity of ASK1 but does not require LATS2 kinase activity. This work identifies a novel role for LATS2 as a positive regulator of the ASK1–MKK–JNK signaling pathway and establishes a kinase-independent function of LATS2 that may be part of the intricate regulatory system for cellular response to diverse stress signals.

Macrophage-Derived Exosomal miR-31-5p Promotes Oral Squamous Cell Carcinoma Tumourigenesis Through the Large Tumor Suppressor 2-Mediated Hippo Signalling Pathway

2021 ◽  
Vol 17 (5) ◽  
pp. 822-837
Author(s):  
Yi Yuan ◽  
Zeyu Wang ◽  
Mengqi Chen ◽  
Yang Jing ◽  
Wei Shu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Suppressor ◽  
Oral Squamous Cell Carcinoma ◽  
M2 Macrophage ◽  
Hippo Signaling ◽  
M2 Macrophages ◽  
Large Tumor ◽  
Hippo Signaling Pathway ◽  
Exosomal Mirnas ◽  
Large Tumor Suppressor

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR- 31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.

scholarly journals MicroRNA miR-4709-3p targets Large Tumor Suppressor Kinase 2 (LATS2) and induces obstructive renal fibrosis through Hippo signaling

Bioengineered ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 12357-12371
Author(s):  
Zexiang Jiang ◽  
Weiping Xia ◽  
Guoyu Dai ◽  
Bo Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Renal Fibrosis ◽  
Hippo Signaling ◽  
Large Tumor ◽  
Large Tumor Suppressor

scholarly journals The Tumor-Suppressor Gene fat Controls Tissue Growth Upstream of Expanded in the Hippo Signaling Pathway

2006 ◽  
Vol 16 (21) ◽  
pp. 2081-2089 ◽  
Author(s):  
Elizabeth Silva ◽  
Yonit Tsatskis ◽  
Laura Gardano ◽  
Nic Tapon ◽  
Helen McNeill
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Signaling Pathway ◽  
Suppressor Gene ◽  
Tissue Growth ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1

Oncogene ◽  
2019 ◽  
Vol 39 (5) ◽  
pp. 1125-1139 ◽  
Author(s):  
Jianxiong Ji ◽  
Kaikai Ding ◽  
Tao Luo ◽  
Ran Xu ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Signaling Pathway ◽  
Transmembrane Protein ◽  
Hippo Pathway ◽  
Ectopic Expression ◽  
Hippo Signaling ◽  
Human Gliomas ◽  
Hippo Signaling Pathway ◽  
The Hippo Pathway

Abstract The Hippo signaling pathway controls organ development and is also known, in cancer, to have a tumor suppressing role. Within the Hippo pathway, we here demonstrate, in human gliomas, a functional interaction of a transmembrane protein, prostate transmembrane protein, androgen induced 1 (PMEPA1) with large tumor suppressor kinase 1 (LATS1). We show that PMEPA1 is upregulated in primary human gliomas. The PMEPA1 isoform PMEPA1a was predominantly expressed in glioma specimens and cell lines, and ectopic expression of the protein promoted glioma growth and invasion in vitro and in an orthotopic xenograft model in nude mice. In co-immunoprecipitation experiments, PMEPA1a associated with the Hippo tumor suppressor kinase LATS1. This interaction led to a proteasomal degradation of LATS1 through recruitment of the ubiquitin ligase, neural precursor cell expressed, developmentally downregulated 4 (NEDD4), which led to silencing of Hippo signaling. Alanine substitution in PMEPA1a at PY motifs resulted in failed LATS1 degradation. Targeting of a downstream component in the Hippo signaling pathway, YAP, with shRNA, interfered with the growth promoting activities of PMEPA1a in vitro and in vivo. In conclusion, the presented work shows that PMEPA1a contributes to glioma progression by a dysregulation of the Hippo signaling pathway and thus represents a promising target for the treatment of gliomas.

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