PMID- 25833829
OWN - NLM
STAT- MEDLINE
DCOM- 20160123
LR  - 20220318
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 75
IP  - 7
DP  - 2015 Apr 1
TI  - PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes 
      Malignant Invasion.
PG  - 1287-97
LID - 10.1158/0008-5472.CAN-14-2444 [doi]
AB  - Correct apicobasal polarization and intercellular adhesions are essential for the 
      appropriate development of normal epithelia. Here, we investigated the 
      contribution of the cell polarity regulator PARD3 to the development of lung 
      squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 
      8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes 
      in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in 
      the ability to mediate formation of tight junctions and actin-based protrusions, 
      bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell 
      confluence. Thus, PARD3 alterations prevented the formation of contacts between 
      neighboring cells and the subsequent downstream signaling. Notably, 
      reconstituting PAR3 activity in vivo reduced tumor-invasive and metastatic 
      properties. Our findings define PARD3 as a recurrently inactivated cell polarity 
      regulator in LSCC that affects tumor aggressiveness and metastasis.
CI  - (c)2015 American Association for Cancer Research.
FAU - Bonastre, Ester
AU  - Bonastre E
AD  - Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge 
      Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, 
      Spain.
FAU - Verdura, Sara
AU  - Verdura S
AD  - Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge 
      Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, 
      Spain.
FAU - Zondervan, Ilse
AU  - Zondervan I
AD  - MRC-Holland, Willem Schoutenstraat, the Netherlands.
FAU - Facchinetti, Federica
AU  - Facchinetti F
AD  - Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, 
      Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
FAU - Lantuejoul, Sylvie
AU  - Lantuejoul S
AD  - Department of Pathology, Institut Albert Bonniot, INSERM U823, University Joseph 
      Fourier, CHU, Grenoble Hopital Michallon, Grenoble, France.
FAU - Chiara, Maria Dolores
AU  - Chiara MD
AD  - Department of Otolaryngology of the Hospital Universitario Central de Asturias, 
      Oviedo, Spain.
FAU - Rodrigo, Juan Pablo
AU  - Rodrigo JP
AD  - Department of Otolaryngology of the Hospital Universitario Central de Asturias, 
      Oviedo, Spain.
FAU - Carretero, Julian
AU  - Carretero J
AD  - Department of Physiology, Faculty of Medicine and Odontology, University of 
      Valencia, Spain.
FAU - Condom, Enric
AU  - Condom E
AD  - Pathology Department, Bellvitge Hospital, Hospitalet de Llobregat, Barcelona, 
      Spain.
FAU - Vidal, Agustin
AU  - Vidal A
AD  - Pathology Department, Bellvitge Hospital, Hospitalet de Llobregat, Barcelona, 
      Spain.
FAU - Sidransky, David
AU  - Sidransky D
AD  - Departments of Otolaryngology-Head and Neck Surgery, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland.
FAU - Villanueva, Alberto
AU  - Villanueva A
AD  - Translational Research Laboratory, Catalan Institute of Oncology (ICO)-IDIBELL, 
      Barcelona, Spain.
FAU - Roz, Luca
AU  - Roz L
AD  - Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, 
      Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
FAU - Brambilla, Elisabeth
AU  - Brambilla E
AD  - Department of Pathology, Institut Albert Bonniot, INSERM U823, University Joseph 
      Fourier, CHU, Grenoble Hopital Michallon, Grenoble, France.
FAU - Savola, Suvi
AU  - Savola S
AD  - MRC-Holland, Willem Schoutenstraat, the Netherlands.
FAU - Sanchez-Cespedes, Montse
AU  - Sanchez-Cespedes M
AD  - Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge 
      Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, 
      Spain. mscespedes@idibell.cat.
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (PARD3 protein, human)
RN  - 0 (RAC1 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma, Squamous Cell/*metabolism/secondary
MH  - Cell Cycle Proteins/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Humans
MH  - Liver Neoplasms/*metabolism/secondary
MH  - Lung Neoplasms/*metabolism/secondary
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice, Nude
MH  - Mutation
MH  - Neoplasm Invasiveness
MH  - Neoplasm Transplantation
MH  - Protein Kinase C/metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Sequence Analysis, DNA
MH  - Transcriptome
MH  - rac1 GTP-Binding Protein/metabolism
PMC - PMC4612637
MID - NIHMS725260
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2015/04/04 06:00
MHDA- 2016/01/24 06:00
PMCR- 2015/10/20
CRDT- 2015/04/03 06:00
PHST- 2015/04/03 06:00 [entrez]
PHST- 2015/04/04 06:00 [pubmed]
PHST- 2016/01/24 06:00 [medline]
PHST- 2015/10/20 00:00 [pmc-release]
AID - 75/7/1287 [pii]
AID - 10.1158/0008-5472.CAN-14-2444 [doi]
PST - ppublish
SO  - Cancer Res. 2015 Apr 1;75(7):1287-97. doi: 10.1158/0008-5472.CAN-14-2444.