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Lkb1‐ a master tumor suppressor (LB108)
Author(s) -
Aube Eric,
Chan Rosanna,
Maynard Alex,
Ortbals Chloe,
Paul Lindsey,
Shome Ria,
Wright Madison,
Kessler Eric,
Tuel Kelly,
Whalen Joseph,
Anant Shrikant
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb108
Subject(s) - ampk , stk11 , cancer research , protein kinase a , pi3k/akt/mtor pathway , scaffold protein , microbiology and biotechnology , mechanistic target of rapamycin , kinase , suppressor , cancer , chemistry , biology , signal transduction , medicine , kras , colorectal cancer
The small intestine is remarkable in that 10 9 epithelial cells are produced every twenty minutes, but cancer rarely develops. This is possible due to the serine/threonine kinase tumor suppressor Liver Kinase B1 (LKB1). Mutations in LKB1 were first linked to the disease Peutz‐Jeghers syndrome in which polyps grow and have a 93% chance of becoming cancerous. Mutations in LKB1 have been linked to several forms of cancer including small intestine, breast, lung, liver, and pancreas. LKB1 forms an active heterotrimer with pseudokinase: STRAD, and scaffolding protein: MO25. LKB1’s primary function is to regulate energy homeostasis through the phosphorylation of the t‐loop structure on adenosine monophosphate protein kinase (AMPK), which mediates the production of ATP when cells enter a state of energy stress. AMPK detects and reacts to differences in the AMP:ATP ratio. AMPK has also been shown to impact several cancer‐related processes. For example, the AMPK‐mTOR signaling pathway is important for inducing cell death within cancer cells. Possible future research includes finding methods of inducing LKB1 activity, which would stimulate the AMPK‐mTOR pathway and diminishes cancer cell proliferation. The CAPS SMART Team (Students Modeling a Research Topic) created physical models of the tumor suppressor protein LKB1 and its target AMPK using 3D printing technology. Grant Funding Source : Supported by grants from the NIH‐SEPA and NIH‐CTSA.