Cancer Biology Project

DLC-1 and RNA Regulatos

Most tissues in our body need to maintain an appropriate balance between stem cell proliferation and differentiation. Insufficient proliferation results in tissue degeneration, while unchecked proliferation is a hallmark of cancer. The work from our lab identified dynein light chain 1 (DLC-1) as an important developmental regulator that controls decisions related to cell proliferation and differentiation in the nematode C. elegans. One interaction partner of DLC-1 is the tumor suppressor protein GLD-1. GLD-1 (and closely related mammalian quaking proteins) are RNA-binding proteins that promote stem cell differentiation during development. Disruption of these genes in either gld-1 mutant worms or quaking mutant mammals results in tumor formation: a germline teratoma or glioblastoma multiforme respectively.  Our results indicate that association with DLC-1 promotes the tumor suppressor function of GLD-1. We are using genetic, biochemical, and molecular approaches to study the cooperation between DLC-1 and GLD-1. Since both DLC-1 and GLD-1 are evolutionarily conserved proteins any new insight into this cooperation will be broadly relevant and significantly advance our understanding of human cancers.