ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP

Xu, Shangcheng; Sun, Xuxu; Sun, Bing; Li, Tao; Wang, Guoliang; Li, Yuantao; Chen, Lai; Liu, Qingxin; Cui, Meng; Zhou, Zizhang

doi:10.1002/1873-3468.12986

Cited by 30 publications

(25 citation statements)

References 32 publications

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“…In patient samples and in preclinical Drosophila models, Arrestin-related domain-containing protein-3 (ARRDC3) was downregulated in the colorectal cancer specimens. ARRDC3 promoted YAP degradation, increased drug sensitivity of the tumor cells and was proposed as a potential drug target (Shen et al, 2018). In another study, loss of Mst1/2 or conditional overexpression of YAP in response to bile acid induced injury in liver cells was shown to cause Hepatocellular carcinoma (HCC) in mice models.…”

Section: Oncogenic Cooperation-models For Cell–cell Interactions Tummentioning

confidence: 99%

Hippo Signaling in Cancer: Lessons From Drosophila Models

Snigdha

Gangwani

Lapalikar

et al. 2019

Front. Cell Dev. Biol.

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Hippo pathway was initially identified through genetic screens for genes regulating organ size in fruitflies. Recent studies have highlighted the role of Hippo signaling as a key regulator of homeostasis, and in tumorigenesis. Hippo pathway is comprised of genes that act as tumor suppressor genes like hippo ( hpo ) and warts ( wts ), and oncogenes like yorkie ( yki ). YAP and TAZ are two related mammalian homologs of Drosophila Yki that act as effectors of the Hippo pathway. Hippo signaling deficiency can cause YAP- or TAZ-dependent oncogene addiction for cancer cells. YAP and TAZ are often activated in human malignant cancers. These transcriptional regulators may initiate tumorigenic changes in solid tumors by inducing cancer stem cells and proliferation, culminating in metastasis and chemo-resistance. Given the complex mechanisms (e.g., of the cancer microenvironment, and the extrinsic and intrinsic cues) that overpower YAP/TAZ inhibition, the molecular roles of the Hippo pathway in tumor growth and progression remain poorly defined. Here we review recent findings from studies in whole animal model organism like Drosophila on the role of Hippo signaling regarding its connection to inflammation, tumor microenvironment, and other oncogenic signaling in cancer growth and progression.

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Section: Oncogenic Cooperation-models For Cell–cell Interactions Tummentioning

confidence: 99%

Hippo Signaling in Cancer: Lessons From Drosophila Models

Snigdha

Gangwani

Lapalikar

et al. 2019

Front. Cell Dev. Biol.

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“…Down-expression of ARRDC3 was first observed in breast cancer, and aberrant expression of ARRDC3 was correspondingly observed in multiple malignant tumors, including renal cell carcinoma, prostate cancer, cervical cancer, and colorectal cancer. [14][15][16] Given previous studies on ARRDC3 in tumors, therefore, we launched a study aiming to detect a correlation between ARRDC3 and OC.…”

Section: Introductionmentioning

confidence: 99%

“…11 Previous reports have reported that the expression of ARRDC3 is associated with various diseases, including inflammatory disease and malignant tumors. [12][13][14][15][16]26 However, information relating to the association between ARRDC3 and OC remained unknown.…”

mentioning

confidence: 99%

ARRDC3 as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer Based on Data Mining

Chen¹,

Tian²,

Chen³

et al. 2021

IJGM

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The dysregulation of arrestin domain containing 3 (ARRDC3) has an important effect on oncogenesis and tumor progression in many cancers, including renal cell carcinoma and breast cancer. However, the role of ARRDC3 in ovarian cancer (OC) has not been reported. Methods: The present study explored the diagnostic and prognostic roles of ARRDC3 in ovarian cancer using GEPIA, ONCOMINE, GEO, and Kaplan-Meier Plotter databases for training and validation. Then, we conducted a stratified analysis for clinicopathological factors using Kaplan-Meier Plotter and GEPIA databases. To further explore the mechanisms, we also used the MIST database to visualize the protein-protein interaction network of ARRDC3 associated with OC. The gene-gene interaction network was visualized by GeneMANIA plugin in Cytoscape 3.8.0 software, and the associated co-expression genes of ARRDC3 were analyzed by the cBioPortal database. The 100 top co-expression genes chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used by the DAVID website. Results: A significant difference in ARRDC3 mRNA expression was found between OC and normal ovary tissues. ARRDC3 could potentially be implicated in the diagnosis of OC. A high ARRDC3 mRNA expression level was associated with poor overall survival and progression-free survival. However, no significance was reported in respect to post progression survival. Except for histology, which had no prognostic value for PPS in stratified analysis, stratified analysis of other factors had prognostic value for OS, PFS, and PPS. Interestingly, we found a positive correlation between ARRDC3 expression and CD8+ T cells, macrophages, neutrophils, and dendritic cells, indicating that ARRDC3 might be associated with immune infiltration of these immune cells. Coexpression genes enrichment analysis found that they were involved in the Renin-angiotensin system pathway. Conclusion: Differentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.

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“…In support of this model, bafilomycin, an inhibitor of lysosomal acidification, increased Yki activity and reversed the effect of Leash over expression. A recent study has confirmed the corresponding Arrdc3-Yap1 interaction in human cells (Shen et al, 2018). Intriguingly, the authors of the Leash study also found that overexpression of Wts could increase the abundance of Yki-positive vesicles in cultured cells, prompting the hypothesis that Yki endolysosomal trafficking may be regulated by the canonical Hippo pathway, rather than operating in parallel to it.…”

Section: Leashmentioning

confidence: 84%

Roles of Membrane and Vesicular Traffic in Regulation of the Hippo Pathway

Verghese

Moberg

2020

Front. Cell Dev. Biol.

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The Hippo pathway is a well conserved signaling cascade that modulates cell proliferation and survival in response to external cues such as cell:cell contact, injury, and nutritional status. Models of the Hippo pathway have evolved from a series of genetic interactions defined in the fruit fly Drosophila melanogaster into a complex series of biochemical mechanisms in which transmembrane and cytoskeletal proteins modulate cytoplasmic phosphatase and kinase activities that converge on the serine/threonine kinase Warts (Wts) to regulate nuclear entry of the co-activator protein Yorkie (Yki; vertebrate Yap1). This pathway is well conserved in human cells and broadly implicated in cancer. Progress in understanding biochemical events within the Hippo pathway highlights a need for improved understanding of the cell biological contexts in which these molecular interactions occur. A significant body of data linking Hippo signaling to membranes and proteins involved in intracellular membrane trafficking raise the possibility that some molecular regulatory events occur on the cytoplasmic face of vesicles. In Drosophila, a Yki-vesicle link was solidified by discoveries that cytoplasmic Yki concentrates at late-endosomes and physically interacts with two endosomal adaptor proteins, Myopic (Mop) and Leash. These two proteins are required for Yki to transit the endolysosomal pathway and be turned over in lysosomes. Molecules involved in recruiting and tethering Yki along this endosomal route are not defined but are predicted to play key roles in regulating Yki levels and thus Hipporesponsiveness of cells. As Wts is recruited to the apical membrane by upstream Hippo components, endosomal internalization could also affect complexes involved in Yki phosphorylation events that alter nucleocytoplasmic shuttling. Recent work has revealed an unexpected, non-transcriptional role of membrane-associated Yki in triggering actinomyosin contractility via the myosin-regulatory light chain Spaghetti squash (Sqh). How Yki interacts with the membrane and controls Sqh is unclear, but this mechanism represents a novel regulatory mechanism based on induced localization of Yki to a specific membrane compartment. These and other data will be discussed as we review data linking Yki to membrane and vesicular traffic in development and homeostasis and speculate on missing elements of these membrane-linked Yki regulatory mechanisms.

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ARRDC3 suppresses colorectal cancer progression through destabilizing the oncoprotein YAP

Cited by 30 publications

References 32 publications

Hippo Signaling in Cancer: Lessons From Drosophila Models

Hippo Signaling in Cancer: Lessons From Drosophila Models

ARRDC3 as a Diagnostic and Prognostic Biomarker for Epithelial Ovarian Cancer Based on Data Mining

Roles of Membrane and Vesicular Traffic in Regulation of the Hippo Pathway

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