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RESEARCH PRODUCT
PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion.
Sylvie LantuejoulSuvi SavolaJuan P. RodrigoDavid SidranskyFederica FacchinettiAlberto VillanuevaMontse Sanchez-cespedesElisabeth BrambillaIlse ZondervanMaría-dolores ChiaraJulian CarreteroLuca RozEnric CondomEster BonastreAgustin VidalSara Verdurasubject
STAT3 Transcription Factorrac1 GTP-Binding ProteinCancer ResearchLung NeoplasmsCellMice NudeRAC1Cell Cycle ProteinsBiologyArticleCell MovementCell Line TumorCell polaritymedicineAnimalsHumansNeoplasm InvasivenessProtein Kinase CAdaptor Proteins Signal TransducingCell ProliferationConfluencyTight junctionBase SequenceCell growthLiver NeoplasmsMembrane ProteinsSequence Analysis DNACell biologymedicine.anatomical_structureOncologyCell cultureMutationCancer researchCarcinoma Squamous CellTranscriptomeIntracellularNeoplasm Transplantationdescription
Abstract 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. Cancer Res; 75(7); 1287–97. ©2015 AACR.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-04-03 | Cancer research |