Loss of the novel tumour suppressor and polarity gene Trim62 (Dear1) synergizes with oncogenic Ras in invasive lung cancer. Issue 1 (16th July 2014)

• Record Type: Journal Article
• Authors: Quintás‐Cardama, Alfonso; Post, Sean M; Solis, Luisa M; Xiong, Shunbin; Yang, Peirong; Chen, Nanyue; Wistuba, Ignacio I; Killary, Ann M; Lozano, Guillermina
• Is Part Of: Journal of pathology. Volume 234:Issue 1(2014)
• Page Start: 108
• Page End: 119
• Publication Date: 2014-07-16
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4385
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4385-abs-0001"> <title>Abstract</title> <p id="path4385-para-0001">Deregulation of cell polarity proteins has been linked to the processes of invasion and metastasis. TRIM62 is a regulator of cell polarity and a tumour suppressor in breast cancer. Here, we demonstrate that human non‐small cell lung cancer lesions show a step‐wise loss of TRIM62 levels during disease progression, which was associated with poor clinical outcomes. To directly examine the role of Trim62 in development of lung cancer, we deleted <italic>Trim62</italic> in a mutant <italic>K‐Ras</italic> mouse model of lung cancer. In this context, haploinsufficiency of <italic>Trim62</italic> synergized with a <italic>K‐RasG12D</italic> mutation to promote invasiveness and disrupt three‐dimensional morphogenesis, both of which are associated with epithelial–mesenchymal transitions. Re‐expression of Trim62 reverted these phenotypes in tumour cell lines. Thus, <italic>Trim62</italic> loss cooperates with <italic>K‐Ras</italic> mutation in tumourigenesis and metastasis <italic>in vivo</italic>, indicating that decreased levels of TRIM62 may play an important role in the evolution of lung cancer. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</p> </abstract>