PMID- 33670622
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 18
TI  - Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human 
      Parathyroid Tumors.
LID - 10.3390/ijms22042016 [doi]
LID - 2016
AB  - 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.
FAU - Tavanti, Giulia Stefania
AU  - Tavanti GS
AUID- ORCID: 0000-0002-3951-3044
AD  - Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 
      20161 Milan, Italy.
AD  - Department of Biomedical, Surgical and Dental Sciences, University of Milan, 
      20122 Milan, Italy.
FAU - Verdelli, Chiara
AU  - Verdelli C
AD  - Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 
      20161 Milan, Italy.
FAU - Morotti, Annamaria
AU  - Morotti A
AUID- ORCID: 0000-0002-4247-4365
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico, 20122 Milan, Italy.
FAU - Maroni, Paola
AU  - Maroni P
AUID- ORCID: 0000-0002-3444-9338
AD  - Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Istituto 
      Ortopedico Galeazzi, 20161 Milan, Italy.
FAU - Guarnieri, Vito
AU  - Guarnieri V
AD  - Division of Medical Genetics, Fondazione IRCCS Ospedale Casa Sollievo della 
      Sofferenza, 71013 San Giovanni Rotondo, Italy.
FAU - Scillitani, Alfredo
AU  - Scillitani A
AD  - Endocrinology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San 
      Giovanni Rotondo, Italy.
FAU - Silipigni, Rosamaria
AU  - Silipigni R
AD  - Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico, 20122 Milan, Italy.
FAU - Guerneri, Silvana
AU  - Guerneri S
AD  - Medical Genetics Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico, 20122 Milan, Italy.
FAU - Maggiore, Riccardo
AU  - Maggiore R
AUID- ORCID: 0000-0002-2869-9859
AD  - Endocrine Surgery, IRCCS Ospedale San Raffaele, 20123 Milan, Italy.
FAU - Mari, Gilberto
AU  - Mari G
AD  - Endocrine Surgery, IRCCS Ospedale San Raffaele, 20123 Milan, Italy.
FAU - Vicentini, Leonardo
AU  - Vicentini L
AD  - Endocrine Surgery, IRCCS Istituto Auxologico, 20122 Milan, Italy.
FAU - Dalino Ciaramella, Paolo
AU  - Dalino Ciaramella P
AD  - Endocrinology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, 
      Italy.
FAU - Vaira, Valentina
AU  - Vaira V
AUID- ORCID: 0000-0003-4416-6216
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico, 20122 Milan, Italy.
AD  - Department of Pathophysiology and Organ Transplantation, University of Milan, 
      20122 Milan, Italy.
FAU - Corbetta, Sabrina
AU  - Corbetta S
AUID- ORCID: 0000-0001-8140-3175
AD  - Department of Biomedical, Surgical and Dental Sciences, University of Milan, 
      20122 Milan, Italy.
AD  - Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, 20161 
      Milan, Italy.
LA  - eng
GR  - Italian Ministry of Health/Italian Ministry of Health/
GR  - Bando Giovani Ricercatori SIOMMMS 2018/Bando Giovani Ricercatori SIOMMMS 2018/
PT  - Journal Article
DEP - 20210218
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (2-methyl-1-((4-methyl-5-isoquinolinyl)sulfonyl)homopiperazine)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amides)
RN  - 0 (MEN1 protein, human)
RN  - 0 (N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine)
RN  - 0 (Phenethylamines)
RN  - 0 (Propylamines)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - 138381-45-0 (Y 27632)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.1.- (LATS1 protein, human)
RN  - EC 2.7.1.11 (LATS2 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
MH  - Adaptor Proteins, Signal Transducing/*genetics/metabolism
MH  - Amides/pharmacology
MH  - Cell Nucleus/drug effects/metabolism
MH  - Gene Expression/drug effects
MH  - HEK293 Cells
MH  - Humans
MH  - Parathyroid Glands/*metabolism
MH  - Parathyroid Neoplasms/*genetics/metabolism
MH  - Phenethylamines/pharmacology
MH  - Propylamines/pharmacology
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Pyridines/pharmacology
MH  - RNA Interference
MH  - Receptors, Calcium-Sensing/agonists/*genetics/metabolism
MH  - Transcription Factors/*genetics/metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/genetics/metabolism
MH  - YAP-Signaling Proteins
MH  - rho-Associated Kinases/antagonists & inhibitors/metabolism
PMC - PMC7922006
OTO - NOTNLM
OT  - CASR
OT  - LATS1/2
OT  - MEN1
OT  - YAP1
OT  - parathormone
OT  - parathyroid tumors
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/20 06:00
PMCR- 2021/02/18
CRDT- 2021/03/06 01:08
PHST- 2020/12/24 00:00 [received]
PHST- 2021/02/15 00:00 [revised]
PHST- 2021/02/16 00:00 [accepted]
PHST- 2021/03/06 01:08 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2021/02/18 00:00 [pmc-release]
AID - ijms22042016 [pii]
AID - ijms-22-02016 [pii]
AID - 10.3390/ijms22042016 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 18;22(4):2016. doi: 10.3390/ijms22042016.