Q:A Tumor suppressor function of Lkb1 is linked to regulation of epithelial integrity
نویسندگان
چکیده
Institute of Biomedicine and Genome-Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, 00014, Helsinki, Finland; Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland; Department of Anatomy, University of California, San Francisco, CA 94143; and Department of Immunology and Pathology, Haartman Institute, University of Helsinki, 00014, Helsinki, Finland
منابع مشابه
Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity.
Although loss of epithelial integrity is a hallmark of advanced cancer, it remains poorly understood whether genetic alterations corrupting this integrity causally facilitate tumorigenesis. We show that conditional deletion of tumor suppressor gene Lkb1 (Par-4) in the mammary gland compromises epithelial integrity manifested by mislocalization of cell polarity markers, lateralization of tight j...
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LKB1 kinase is a tumor suppressor that is causally linked to Peutz-Jeghers syndrome. In complex with the pseudokinase STRAD and the scaffolding protein MO25, LKB1 phosphorylates and activates AMPK family kinases, which mediate many cellular processes. The prototypical family member AMPK regulates cell energy metabolism and epithelial apicobasal polarity. This latter event is also dependent on E...
متن کاملLKB1 and AMPK maintain epithelial cell polarity under energetic stress
LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5'monophosphate-activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1-...
متن کاملThe LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue. LKB1 is a tumor suppressor that controls cell polarity, metabolism, and microtubule stability. Here, we show that germline LKB1 mutation in mice impairs spindle orientation in cells of the upper gastrointestinal tract and causes dramatic mislocalization of the LKB1 substra...
متن کاملThe molecular mechanisms that underlie the tumor suppressor function of LKB1.
Germline mutations of the LKB1 tumor suppressor gene result in Peutz-Jeghers syndrome (PJS) characterized by intestinal hamartomas and increased incidence of epithelial cancers. Inactivating mutations in LKB1 have also been found in certain sporadic human cancers and with particularly high frequency in lung cancer. LKB1 has now been demonstrated to play a crucial role in pulmonary tumorigenesis...
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