Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors

Giulia Stefania Tavanti; Chiara Verdelli; Annamaria Morotti; Paola Maroni; Vito Guarnieri; Alfredo Scillitani; Rosamaria Silipigni; Silvana Guerneri; Riccardo Maggiore; Gilberto Mari; Leonardo Vicentini; Paolo Dalino Ciaramella; Valentina Vaira; Sabrina Corbetta

doi:10.3390/ijms22042016

journal article Open Access Feb 18, 2021

Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors

Giulia Stefania Tavanti

Chiara Verdelli Annamaria Morotti

Paola Maroni

Vito Guarnieri Alfredo Scillitani Rosamaria Silipigni Silvana Guerneri Riccardo Maggiore

Gilberto Mari Leonardo Vicentini Paolo Dalino Ciaramella Valentina Vaira

Sabrina Corbetta

International Journal of Molecular Sciences Vol. 22 No. 4 pp. 2016 · MDPI AG

View at Publisher Save 10.3390/ijms22042016

Abstract

The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1(MEN1), while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61, CTGF, and WNT5A, and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.

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Details

Published: Feb 18, 2021
Vol/Issue: 22(4)
Pages: 2016
License: View

Authors

G

Giulia Stefania Tavanti

Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy

C

Chiara Verdelli

Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy

A

Annamaria Morotti

Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy

P

Paola Maroni

Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy

V

Vito Guarnieri

Division of Medical Genetics, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy

A

Alfredo Scillitani

Endocrinology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy

R

Rosamaria Silipigni

Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy

S

Silvana Guerneri

Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy

R

Riccardo Maggiore

Endocrine Surgery, IRCCS Ospedale San Raffaele, 20123 Milan, Italy

G

Gilberto Mari

Endocrine Surgery, IRCCS Ospedale San Raffaele, 20123 Milan, Italy

L

Leonardo Vicentini

Endocrine Surgery, IRCCS Istituto Auxologico, 20122 Milan, Italy

P

Paolo Dalino Ciaramella

Endocrinology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy

V

Valentina Vaira

Division of Pathology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy; Department of Pathophysiology and Organ Transplantation, University of Milan, 20122 Milan, Italy

S

Sabrina Corbetta

Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy; Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy

Funding

Italian Ministry of Health Award: Italian Ministry of Health

Bando Giovani Ricercatori SIOMMMS 2018 Award: Bando Giovani Ricercatori SIOMMMS 2018

Cite This Article

Giulia Stefania Tavanti, Chiara Verdelli, Annamaria Morotti, et al. (2021). Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors. International Journal of Molecular Sciences, 22(4), 2016. https://doi.org/10.3390/ijms22042016

Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors

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