PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion

被引：43

作者：

Bonastre, Ester ^{[1
]}

Verdura, Sara ^{[1
]}

Zondervan, Ilse ^{[2
]}

Facchinetti, Federica ^{[3
]}

Lantuejoul, Sylvie ^{[4
]}

Dolores Chiara, Maria ^{[5
]}

Pablo Rodrigo, Juan ^{[5
]}

Carretero, Julian ^{[6
]}

Condom, Enric ^{[7
]}

Vidal, Agustin ^{[7
]}

Sidransky, David ^{[8
,9
]}

Villanueva, Alberto ^{[10
]}

Roz, Luca ^{[3
]}

Brambilla, Elisabeth ^{[4
]}

Savola, Suvi ^{[2
]}

Sanchez-Cespedes, Montse ^{[1
]}

机构：

[1] Hosp Llobregat, Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Genes & Canc Grp, Barcelona 08908, Spain

[2] MRC Holland, Amsterdam, Netherlands

[3] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Tumor Genom Unit, Milan, Italy

[4] Univ Grenoble 1, Inst Albert Bonniot, Grenoble Hop Michallon, Dept Pathol,CHU,INSERM U823, Grenoble, France

[5] Hosp Univ Cent Asturias, Dept Otolaryngol, Oviedo, Spain

[6] Univ Valencia, Fac Med & Odontol, Dept Physiol, E-46003 Valencia, Spain

[7] Hosp Llobregat, Bellvitge Hosp, Pathol Dept, Barcelona 08908, Spain

[8] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head, Baltimore, MD USA

[9] Johns Hopkins Univ, Sch Med, Dept Neck Surg, Baltimore, MD USA

[10] Catalan Inst Oncol ICO IDIBELL, Translat Res Lab, Barcelona, Spain

来源：

CANCER RESEARCH | 2015年 / 75卷 / 07期

关键词：

POLARITY PROTEINS; CANCER; COMPLEX; MUTATIONS; GENE; ACTIVATION; DOMAIN; PAR-3; AMPLIFICATION; LOCALIZATION;

D O I：

10.1158/0008-5472.CAN-14-2444

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C)2015 AACR.

引用

页码：1287 / 1297

页数：11

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