Abstract 3940: Inactivation of the PARD3 gene is a recurrent event in lung squamous cell carcinomas and affects STAT3 activity and tumor invasiveness

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.3940-3940
• Main Authors: Bonastre, Ester, Verdura, Sara, Zondervan, Ilse, Facchinetti, Federica, Lantuejoul, Sylvie, Chiara, Maria Dolores, Rodrigo, Juan Pablo, Carretero, Julian, Sidransky, David, Villanueva, Alberto, Condom, Enric, Vidal, Agustin, Roz, Luca, Brambilla, Elisabeth, Savola, Suvi, Sanchez-Cespedes, Montse
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-3940

Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the partitioning defective 3 gene, PARD3, to the carcinogenesis of lung squamous cell carcinomas (LSCCs). Tumor-specific PARD3 alterations were found in eight per cent of the tumors, placing PARD3 among the most common tumor suppressor genes in LSCC. Some PAR3 mutant proteins prevented the formation of contacts between neighboring cells, i.e. had reduced ability to form tight junctions and actin-based protrusions. This affected subsequent downstream signaling, i.e. binding to aPKC and activation of RAC1. Further, we discovered that PAR3 wild type triggered the expression of cell adhesion and polarity-related transcripts and the activation of STAT3, by cell confluence. Finally, restitution of PAR3 in vivo significantly reduced the formation of metastasis. In conclusion, PARD3 is recurrently inactivated in LSCC and its deficiency contributes to the tumor aggressiveness. Citation Format: Ester Bonastre, Sara Verdura, Ilse Zondervan, Federica Facchinetti, Sylvie Lantuejoul, Maria Dolores Chiara, Juan Pablo Rodrigo, Julian Carretero, David Sidransky, Alberto Villanueva, Enric Condom, Agustin Vidal, Luca Roz, Elisabeth Brambilla, Suvi Savola, Montse Sanchez-Cespedes. Inactivation of the PARD3 gene is a recurrent event in lung squamous cell carcinomas and affects STAT3 activity and tumor invasiveness. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3940. doi:10.1158/1538-7445.AM2015-3940