PARD3 inactivation in lung squamous cell carcinomas impairs STAT3 and promotes malignant invasion

Ester Bonastre, Sara Verdura, Ilse Zondervan, Federica Facchinetti, Sylvie Lantuejoul, Maria Dolores Chiara, Juan Pablo Rodrigo, Julian Carretero, Enric Condom, Agustin Vidal, David Sidransky, Alberto Villanueva, Luca Roz, Elisabeth Brambilla, Suvi Savola, Montse Sanchez-Cespedes

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1287-1297
Number of pages11
JournalCancer Research
Volume75
Issue number7
DOIs
Publication statusPublished - Apr 1 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bonastre, E., Verdura, S., Zondervan, I., Facchinetti, F., Lantuejoul, S., Chiara, M. D., Rodrigo, J. P., Carretero, J., Condom, E., Vidal, A., Sidransky, D., Villanueva, A., Roz, L., Brambilla, E., Savola, S., & Sanchez-Cespedes, M. (2015). PARD3 inactivation in lung squamous cell carcinomas impairs STAT3 and promotes malignant invasion. Cancer Research, 75(7), 1287-1297. https://doi.org/10.1158/0008-5472.CAN-14-2444