Primary cilium regulates cell migration and mechanical contraction in mesothelioma cell models

Author(s):  
Ourania Kotsiou ◽  
Rajesh Jagirdar ◽  
Erasmia Rouka ◽  
Eleanna Pitaraki ◽  
Konstantinos Gourgoulianis ◽  
...  
2020 ◽  
Vol 11 (8) ◽  
Author(s):  
Zhen Quan ◽  
Ting Li ◽  
Yang Xia ◽  
Jiayu Liu ◽  
Zhongbo Du ◽  
...  

Abstract Androgen receptor (AR) signaling is a major driver of prostate cancer (CaP). Although most therapies targeting AR are initially effective in CaP patients, drug resistance is inevitable, mainly because of the inappropriate re-activation of AR pathway. However, the underlying mechanisms remain largely unknown. Here, we found that phospholipase C epsilon (PLCɛ) was highly expressed in CaP samples, and was closely associated with AR signaling activities. PLCɛ depletion triggered enhanced autophagic activities via AMPK/ULK1 pathway, causing autophagy-mediated AR degradation and inhibition of AR nuclear translocation. This subsequently reduced AR signals in CaP and inhibited AR-driven cell migration/invasion. Furthermore, a positive correlation between PLCɛ and AR signaling activity was also observed in bicalutamide-resistant CaP samples and in AR-antagonist-resistant CaP cell models. PLCɛ depletion resulted in the failure to establish AR-antagonist-resistant CaP cell lines, and hindered the metastatic prowess of already established ones. These findings suggest that PLCɛ-mediated autophagic activity alteration is indispensible for the functionality of AR signaling and for CaP development.


BioScience ◽  
2014 ◽  
Vol 64 (12) ◽  
pp. 1115-1125 ◽  
Author(s):  
Iben Rønn Veland ◽  
Louise Lindbæk ◽  
Søren Tvorup Christensen

2018 ◽  
Vol 24 (15) ◽  
pp. 3729-3740 ◽  
Author(s):  
Viktoria Laszlo ◽  
Zsuzsanna Valko ◽  
Ildiko Kovacs ◽  
Judit Ozsvar ◽  
Mir Alireza Hoda ◽  
...  

2020 ◽  
Vol 6 (36) ◽  
pp. eaba3992 ◽  
Author(s):  
Julie Stoufflet ◽  
Maxime Chaulet ◽  
Mohamed Doulazmi ◽  
Coralie Fouquet ◽  
Caroline Dubacq ◽  
...  

The primary cilium (PC) is a small centrosome-assembled organelle, protruding from the surface of most eukaryotic cells. It plays a key role in cell migration, but the underlying mechanisms are unknown. Here, we show that the PC regulates neuronal migration via cyclic adenosine 3’-5’ monosphosphate (cAMP) production activating centrosomal protein kinase A (PKA). Biosensor live imaging revealed a periodic cAMP hotspot at the centrosome of embryonic, postnatal, and adult migrating neurons. Genetic ablation of the PC, or knockdown of ciliary adenylate cyclase 3, caused hotspot disappearance and migratory defects, with defective centrosome dynamics and altered nucleokinesis. Delocalization of PKA from the centrosome phenocopied the migratory defects. Our results show that the PC and centrosome form a single cAMP signaling unit dynamically regulating migration, further highlighting the centrosome as a signaling hub.


2010 ◽  
Vol 25 (2-3) ◽  
pp. 279-292 ◽  
Author(s):  
Linda Schneider ◽  
Michael Cammer ◽  
Jonathan Lehman ◽  
Sonja Nielsen ◽  
Charles Guerra ◽  
...  

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4033 ◽  
Author(s):  
Tove Kirkegaard ◽  
Mikail Gögenur ◽  
Ismail Gögenur

Background The perioperative period is important for patient outcome. Colorectal cancer surgery can lead to metastatic disease due to release of disseminated tumor cells and the induction of surgical stress response. To explore the overall effects on surgically-induced changes in serum composition, in vitro model systems are useful. Methods A systematic search in PubMed and EMBASE was performed to identify studies describing in vitro models used to investigate cancer cell growth/proliferation, cell migration, cell invasion and cell death of serum taken pre- and postoperatively from patients undergoing colorectal tumor resection. Results Two authors (MG and TK) independently reviewed 984 studies and identified five studies, which fulfilled the inclusion criteria. Disagreements were solved by discussion. All studies investigated cell proliferation and cell invasion, whereas three studies investigated cell migration, and only one study investigated cell death/apoptosis. One study investigated postoperative peritoneal infection due to anastomotic leak, one study investigated mode of anesthesia (general anesthesia with volatile or intravenous anesthetics), and one study investigated preoperative intervention with granulocyte macrophage colony stimulating factor (GMCSF). In all studies an increased proliferation, cell migration and invasion was demonstrated after surgery. Anesthetics with propofol and intervention with GMCSF significantly reduced postoperative cell proliferation, whereas peritoneal infection enhanced the invasive capability of tumor cells. Conclusion This study suggests that in vitro cell models are useful and reliable tools to explore the effect of surgery on colorectal cancer cell proliferation and metastatic ability. The models should therefore be considered as additional tests to investigate the effects of perioperative interventions.


2019 ◽  
Author(s):  
Julie Stoufflet ◽  
Maxime Chaulet ◽  
Mohamed Doulazmi ◽  
Coralie Fouquet ◽  
Caroline Dubacq ◽  
...  

The primary cilium (PC) is a small centrosome-assembled organelle, protruding from the surface of most eukaryotic cells. It plays a key role in cell migration, but the underlying mechanisms are unknown. Here, we show that the PC regulates neuronal migration via cAMP production activating centrosomal Protein Kinase A (PKA). Biosensor live-imaging revealed a periodic cAMP hotspot at the centrosome of embryonic, postnatal and adult migrating neurons. Genetic ablation of the PC, or knock-down of ciliary Adenylate Cyclase 3, caused hotspot disappearance and migratory defects, with defective centrosome/nucleus coupling and altered nucleokinesis. Delocalization of PKA from the centrosome phenocopied the migratory defects. Our results show that the PC and centrosome form a single cAMP-signaling unit dynamically regulating migration, further highlighting the centrosome as a signaling hub.


Author(s):  
Ourania Kotsiou ◽  
Rajesh Jagirdar ◽  
Erasmia Rouka ◽  
Eleanna Pitaraki ◽  
Konstantinos Gourgoulianis ◽  
...  

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