The Chemosensory Function of Primary Cilia Regulates Cholangiocyte Migration, Invasion, and Tumor Growth

Mansini, Adrián P.; Peixoto, Estanislao; Jin, Sujeong; Richard, Seth; Gradilone, Sergio A.

doi:10.1002/hep.30308

Cited by 28 publications

(29 citation statements)

References 48 publications

(86 reference statements)

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“…A study on P2Y 11 functions in cholangiocytes and CCA eloquently illustrated how a simple change in the cellular context, here the absence or presence of chemosensory cilia, can lead to opposing cell responses in the same cell type [65]. Cholangiocytes express primary cilia that act as mechano-, chemo-, and osmosensors [66].…”

Section: P2y 6 Receptor Promotes Pancreatic and Colorectal Cancer Tummentioning

confidence: 99%

Reviewing the role of P2Y receptors in specific gastrointestinal cancers

Dagenais-Bellefeuille

Molle

Gendron

2019

Purinergic Signalling

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Extracellular nucleotides are important intercellular signaling molecules that were found enriched in the tumor microenvironment. In fact, interfering with G protein-coupled P2Y receptor signaling has emerged as a promising therapeutic alternative to treat aggressive and difficult-to-manage cancers such as those affecting the gastrointestinal system. In this review, we will discuss the functions of P2Y receptors in gastrointestinal cancers with an emphasis on colorectal, hepatic, and pancreatic cancers. We will show that P2Y 2 receptor up-regulation increases cancer cell proliferation, tumor growth, and metastasis in almost all studied gastrointestinal cancers. In contrast, we will present P2Y 6 receptor as having opposing roles in colorectal cancer vs. gastric cancer. In colorectal cancer, the P2Y 6 receptor induces carcinogenesis by inhibiting apoptosis, whereas P2Y 6 suppresses gastric cancer tumor growth by reducing β-catenin transcriptional activity. The contribution of the P2Y 11 receptor in the migration of liver and pancreatic cancer cells will be compared to its normal inhibitory function on this cellular process in ciliated cholangiocytes. Hence, we will demonstrate that the selective inhibition of the P2Y 12 receptor activity in platelets was associated to a reduction in the risk of developing colorectal cancer and metastasis formation. We will succinctly review the role of P2Y 1 , P2Y 4 , P2Y 13 , and P2Y 14 receptors as the knowledge for these receptors in gastrointestinal cancers is sparse. Finally, redundant ligand selectivity, nucleotide high lability, cell context, and antibody reliability will be presented as the main difficulties in defining P2Y receptor functions in gastrointestinal cancers.

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Section: P2y 6 Receptor Promotes Pancreatic and Colorectal Cancer Tummentioning

confidence: 99%

Reviewing the role of P2Y receptors in specific gastrointestinal cancers

Dagenais-Bellefeuille

Molle

Gendron

2019

Purinergic Signalling

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“…Therefore, the effect of ATP on cell migration, invasion, and proliferation was explored. The data suggest that ATP inhibits migration and invasion in a cilia-dependent manner, with an inhibitory effect in the presence of primary cilia but a stimulatory effect in the absence of primary cilia [107].…”

Section: Primary Cilium In Cell Signaling and Sensingmentioning

confidence: 87%

Insight on the role of RKIP in cancer through key protein partners and cellular protrusions

Schoentgen

2020

Prognostic and Therapeutic Applications of RKIP in Cancer

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Previously, by comparing the cellular processes in which RKIP is implied and by analyzing the function of numerous molecular partners, we have suggested that RKIP may participate in regulating actin reorganization and membrane remodeling. Here, based on the role of RKIP in cancer, we describe the cellular function of five important partners of RKIP (GRK2, IQGAP, MT1-MMP, LC3 and Rab8). By their own activity, they may explain, at least in part, the multiple functions of RKIP as they are key actors in diverse cellular processes. All these proteins play a role in the formation or maturation of cellular protrusions such primary cilium, lamellipodia, filopodia or invadopodia. Considering the close relationship between actin cytoskeleton and membrane during cell migration, we suggest that a major role of RKIP in cells is likely to associate with main molecular assemblies, in order to drive the cortical actin/membrane complex in response to signaling pathways. In cancer cells, because of the lack of RKIP, this important regulation is lost.

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“…HDAC6 is another isoform of HDACs that is considered as enhancing CCA cell growth [58]. Inhibitors of HDAC6 such as ACY1215 and tubastatin-A significantly inhibited CCA cell growth in vitro and in vivo [28,71,72].…”

Section: Ciliary Assemblymentioning

confidence: 99%

Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Pant

Peixoto

Richard

et al. 2020

Cells

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Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many cellular proteins including histones may undergo a series of enzyme-mediated post-translational modifications including acetylation, methylation, phosphorylation, sumoylation, and crotonylation. Histone deacetylases (HDACs) play an important role in regulating epigenetic maintenance and modifications of their targets, which in turn exert critical impacts on chromatin structure, gene expression, and stability of proteins. As such, HDACs constitute a group of potential therapeutic targets for CCA. The aim of this review was to summarize the role that HDACs perform in regulating epigenetic changes, tumor development, and their potential as therapeutic targets for CCA.

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The Chemosensory Function of Primary Cilia Regulates Cholangiocyte Migration, Invasion, and Tumor Growth

Cited by 28 publications

References 48 publications

Reviewing the role of P2Y receptors in specific gastrointestinal cancers

Reviewing the role of P2Y receptors in specific gastrointestinal cancers

Insight on the role of RKIP in cancer through key protein partners and cellular protrusions

Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

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