Publication date: December 2017
Source:Neoplasia, Volume 19, Issue 12
Author(s): Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer. In EGFR-addicted lung cancer cell lines (HCC4006 and HCC827) rendered resistant to several EGFR inhibitors, we observed that resistance was associated to YAP activation. Indeed, YAP silencing impaired the maintenance of resistance, while YAP overexpression decreased the responsiveness to EGFR inhibitors in sensitive parental cells. In our models, we identified the AXL tyrosine kinase receptor as the main YAP downstream effector responsible for sustaining YAP-driven resistance: in fact, AXL expression was YAP dependent, and pharmacological or genetic AXL inhibition restored the sensitivity of resistant cells to the anti-EGFR drugs. Notably, YAP overactivation and AXL overexpression were identified in a lung cancer patient upon acquisition of resistance to EGFR TKIs, highlighting the clinical relevance of our in vitro results. The reported data demonstrate that YAP and its downstream target AXL play a crucial role in resistance to EGFR TKIs and suggest that a combined inhibition of EGFR and the YAP/AXL axis could be a good therapeutic option in selected NSCLC patients.
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Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Η λίστα ιστολογίων μου
Κυριακή 12 Νοεμβρίου 2017
YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC
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- Potential for health care cost savings with preope...
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- Reviewers 2017
- miR-140-5p-mediated regulation of the proliferatio...
- Volume content for 2017
- Author Guidelines
- Oral health-related quality of life, measured usin...
- Asthma versus chronic obstructive pulmonary diseas...
- Update on questionnaires for assessing adherence t...
- Drug-induced anaphylaxis: is it an epidemic?
- Extent and consequences of inadequate disease cont...
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- Keratosis follicularis squamosa (Dohi) successfull...
- Laparoscopic repair of a right diaphragmatic herni...
- Knowledge, behavior and attitudes of dental practi...
- Combination Vismodegib and Photodynamic Therapy fo...
- Short-term effects of adjunctive antimicrobial pho...
- A new screening method to detect proximal dental c...
- Secretion of the angiogenic factor VEGF after phot...
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- Photodynamic therapy using a cytotoxic photosensit...
- IDIOPATHIC ELASTOSIS PERFORANS SERPIGINOSA WITH SA...
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- Photodynamic therapy for the treatment of peri-imp...
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- Treatment of oral refractory large area mucosal le...
- Clinical study on clinical operation and post-trea...
- Antimicrobial photodynamic therapy (aPDT) and phot...
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- Programmable LED-based integrating sphere light so...
- Assessing daylight & low-dose rate photodynamic th...
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- Evaluation of the serum zinc level in adult patien...
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- Characterization of sweat induced with pilocarpine...
- Ultrasound with neurostimulation compared with ult...
- Ultrasound with neurostimulation compared with ult...
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- Update on questionnaires for assessing adherence t...
- Drug-induced anaphylaxis: is it an epidemic?
- Ischemia reperfusion injury in aged livers - the e...
- Asthma versus chronic obstructive pulmonary diseas...
- Update on questionnaires for assessing adherence t...
- Drug-induced anaphylaxis: is it an epidemic?
- Prevalence of obesity among adults in Issele-Uku, ...
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- tDCS changes in motor excitability are specific to...
- Early symptom improvement at 10 sessions as a pred...
- Vagus nerve magnetic modulation facilitates dyspha...
- Simultaneous rTMS and psychotherapy in major depre...
- Masthead
- Editorial Board
- Table of Contents
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- Information for Authors
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- Electroconvulsive therapy, depression, the immune ...
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- Simultaneous aerobic exercise and rTMS: Feasibilit...
- Sensory percepts induced by microwire array and DB...
- TLR8 activation and inhibition by guanosine analog...
- Defining the Role of Free Flaps in Partial Breast ...
- Recent advances in melanoma research via “omics” p...
- CaMKIIα expression in a mouse model of NMDAR hypof...
- Diabetes mellitus in a patient with glycogen stora...
- Diabetes mellitus in a patient with glycogen stora...
- Sarcopenia in Peripheral Arterial Disease: Prevale...
- Pain Neurophysiology Education and Therapeutic Exe...
- A systematic review on the effect of serious games...
- Electrophysiological correlates of performance mon...
- Cancer stem cell and its niche in malignant progre...
- Evaluating the association between household air p...
- Atmospheric-pressure chemical purification of deto...
- Monitoring of uranium concentrations in water samp...
- Recovery stress formation in FeMnSi based shape me...
- Experimental and numerical study on soft-hard-soft...
- The utility of oral brush cytology in the early de...
- Equination (inoculation of horsepox): An early alt...
- YAP-Dependent AXL Overexpression Mediates Resistan...
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