LATS tumor suppressor: A new governor of cellular homeostasis

Abstract

Accumulating evidence points to the LATS (Large Tumor Suppressor) family of human tumor suppressors (LATS1 and LATS2) as new resident governors of cellular homeostasis.  Loss of function of either LATS1 or LATS2 leads to a variety of tumor types including soft tissue sarcomas, leukemia, as well as breast, prostate, lung, and esophageal cancers.  Due to their high degree of homology and functional overlap, LATS1 and LATS2 comprise a new tumor suppressor family.  Classically identified within the Hippo-LATS signaling pathway, LATS also acts independently of this pathway, possessing multiple functions including regulation of cell proliferation, cell death, and cell migration, as well as broad governing roles such as transcriptional regulation and maintenance of genetic stability.  Activity of LATS is tightly controlled through various mechanisms including post-translational modifications, differential localization and expression.  Although little is known about the specific underlying mechanisms of these activities, current data suggest that LATS signaling intersects with well-established tumor suppressive or oncogenic pathways including the p53, Ras, or Akt networks.  This review aims to identify what we know about the LATS tumor suppressor family, highlighting LATS1 and LATS2 redundancies or differences in terms of their structure, expression, regulation, and functions, thereby establishing a novel tumor suppressor network.