The Peutz-Jeghers kinase LKB1 suppresses polyp growth from intestinal cells of a proglucagon-expressing lineage in mice

DMM Disease Models and Mechanisms

Volumn 7, Issue 11, 2014, Pages 1275-1286

  Zac Varghese, Sagen ^a   Trapp, Stefan ^a   Richards, Paul ^b   Sayers, Sophie ^a   Sun, Gao ^a   Bloom, Stephen R ^a   Reimann, Frank ^b   Gribble, Fiona M ^b   Rutter, Guy A ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Glucagon; LKB1; Peutz Jeghers

Indexed keywords

PROGLUCAGON; PROTEIN KINASE LKB1; PROTEIN SERINE THREONINE KINASE; STK11 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL LINEAGE; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; GLUCOSE HOMEOSTASIS; GROWTH RATE; INTESTINE CELL; INTESTINE POLYP; MOUSE; NONHUMAN; PEUTZ JEGHERS SYNDROME; PROTEIN EXPRESSION; ANIMAL; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY;

ANIMALIA; MUS;

ANIMALS; EPITHELIAL-MESENCHYMAL TRANSITION; INTESTINAL POLYPS; MICE; MICE, KNOCKOUT; PROGLUCAGON; PROTEIN-SERINE-THREONINE KINASES;

EID: 84919965684     PISSN: 17548403     EISSN: 17548411     Source Type: Journal    
DOI: 10.1242/dmm.014720     Document Type: Article

References (52)

1. Bardeesy, N., Sinha, M., Hezel, A. F., Signoretti, S., Hathaway, N. A., Sharpless, N. E., Loda, M., Carrasco, D. R. and DePinho, R. A. (2002). Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419, 162-167.
2. Barnes, A. P., Lilley, B. N., Pan, Y. A., Plummer, L. J., Powell, A. W., Raines, A. N., Sanes, J. R. and Polleux, F. (2007). LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell 129, 549-563.
3. Beggs, A. D., Latchford, A. R., Vasen, H. F., Moslein, G., Alonso, A., Aretz, S., Bertario, L., Blanco, I., Bülow, S., Burn, J. et al. (2010). Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 59, 975-986.
4. Biancani, P., Zabinski, M. P., Kerstein, M. D. and Behar, J. (1980). Mechanical characteristics of the cat pylorus. Gastroenterology 78, 301-309.
5. Boardman, L. A., Thibodeau, S. N., Schaid, D. J., Lindor, N. M., McDonnell, S. K., Burgart, L. J., Ahlquist, D. A., Podratz, K. C., Pittelkow, M. and Hartmann, L. C. (1998). Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann. Intern. Med. 128, 896-899.
6. Bryant, M. G., Bloom, S. R., Polak, J. M., Hobbs, S., Domschke, W., Domschke, S., Mitznegg, P., Ruppin, H. and Demling, L. (1983). Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine. Gut 24, 114-119.
7. Campbell, J. E. and Drucker, D. J. (2013). Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 17, 819-837.
8. Diakogiannaki, E., Gribble, F. M. and Reimann, F. (2012). Nutrient detection by incretin hormone secreting cells. Physiol. Behav. 106, 387-393.
9. Eissele, R., Göke, R., Willemer, S., Harthus, H. P., Vermeer, H., Arnold, R. and Göke, B. (1992). Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur. J. Clin. Invest. 22, 283-291.
10. Entius, M. M., Keller, J. J., Westerman, A. M., van Rees, B. P., van Velthuysen, M. L., de Goeij, A. F., Wilson, J. H., Giardiello, F. M. and Offerhaus, G. J. (2001). Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. J. Clin. Pathol. 54, 126-131.
11. Fu, A., Ng, A. C., Depatie, C., Wijesekara, N., He, Y., Wang, G. S., Bardeesy, N., Scott, F. W., Touyz, R. M., Wheeler, M. B. et al. (2009). Loss of Lkb1 in adult beta cells increases beta cell mass and enhances glucose tolerance in mice. Cell Metab. 10, 285-295.
12. Giardiello, F. M., Brensinger, J. D., Tersmette, A. C., Goodman, S. N., Petersen, G. M., Booker, S. V., Cruz-Correa, M. and Offerhaus, J. A. (2000). Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119, 1447-1453.
13. Granot, Z., Swisa, A., Magenheim, J., Stolovich-Rain, M., Fujimoto, W., Manduchi, E., Miki, T., Lennerz, J. K., Stoeckert, C. J., Jr, Meyuhas, O. et al. (2009). LKB1 regulates pancreatic beta cell size, polarity, and function. Cell Metab. 10, 296-308.
14. Gruber, S. B., Entius, M. M., Petersen, G. M., Laken, S. J., Longo, P. A., Boyer, R., Levin, A. M., Mujumdar, U. J., Trent, J. M., Kinzler, K. W. et al. (1998). Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res. 58, 5267-5270.
15. Habib, A. M., Richards, P., Cairns, L. S., Rogers, G. J., Bannon, C. A., Parker, H. E., Morley, T. C., Yeo, G. S., Reimann, F. and Gribble, F. M. (2012). Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153, 3054-3065.
16. Hansen, C. F., Vrang, N., Sangild, P. T. and Jelsing, J. (2013). Novel insight into the distribution of L-cells in the rat intestinal tract. Am. J. Transl. Res. 5, 347-358.
17. Herrera, P. L. (2000). Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development 127, 2317-2322.
18. Inoki, K., Zhu, T. and Guan, K. L. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590.
19. Jishage, K., Nezu, J., Kawase, Y., Iwata, T., Watanabe, M., Miyoshi, A., Ose, A., Habu, K., Kake, T., Kamada, N. et al. (2002). Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and polyposis. Proc. Natl. Acad. Sci. USA 99, 8903-8908.
20. Karra, E., Yousseif, A. and Batterham, R. L. (2010). Mechanisms facilitating weight loss and resolution of type 2 diabetes following bariatric surgery. Trends Endocrinol. Metab. 21, 337-344.
21. Katajisto, P., Vaahtomeri, K., Ekman, N., Ventelä, E., Ristimäki, A., Bardeesy, N., Feil, R., DePinho, R. A. and Mäkelä, T. P. (2008). LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis. Nat. Genet. 40, 455-459.
22. Kemphues, K. J., Priess, J. R., Morton, D. G. and Cheng, N. S. (1988). Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311-320.
23. Krstić;, M., Katić;, V., Stojnev, S., Mihailović;, D., Mojsilović;, M., Radovanović;, Z. and Zivković;, V. (2013). Peutz-Jeghers syndrome: quantitative study on enterochromaffin cells in hamartomatous intestine polyps. Srp. Arh. Celok. Lek. 141, 602-607.
24. le Roux, C. W., Borg, C., Wallis, K., Vincent, R. P., Bueter, M., Goodlad, R., Ghatei, M. A., Patel, A., Bloom, S. R. and Aylwin, S. J. (2010). Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann. Surg. 252, 50-56.
25. Leclerc, I., Sun, G., Morris, C., Fernandez-Millan, E., Nyirenda, M. and Rutter, G. A. (2011). AMP-activated protein kinase regulates glucagon secretion from mouse pancreatic alpha cells. Diabetologia 54, 125-134.
26. Lee, C. S., Perreault, N., Brestelli, J. E. and Kaestner, K. H. (2002). Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Genes Dev. 16, 1488-1497.
27. Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G. et al. (2004). LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 23, 833-843.
28. Llewellyn-Smith, I. J., Gnanamanickam, G. J., Reimann, F., Gribble, F. M. and Trapp, S. (2013). Preproglucagon (PPG) neurons innervate neurochemically identified autonomic neurons in the mouse brainstem. Neuroscience 229, 130-143.
29. Luche, H., Weber, O., Nageswara Rao, T., Blum, C. and Fehling, H. J. (2007). Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage tracing studies. Eur. J. Immunol. 37, 43-53.
30. Marx, A., Nugoor, C., Panneerselvam, S. and Mandelkow, E. (2010). Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases. FASEB J. 24, 1637-1648.
31. Mendez, M. G., Kojima, S. and Goldman, R. D. (2010). Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J. 24, 1838-1851.
32. Merchenthaler, I., Lane, M. and Shughrue, P. (1999). Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J. Comp. Neurol. 403, 261-280.
33. Miyoshi, H., Nakau, M., Ishikawa, T. O., Seldin, M. F., Oshima, M. and Taketo, M. M. (2002). Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res. 62, 2261-2266.
34. Nauck, M. A. (2011). Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am. J. Med. 124 Suppl., S3-S18.
35. Parker, H. E., Adriaenssens, A., Rogers, G., Richards, P., Koepsell, H., Reimann, F. and Gribble, F. M. (2012). Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55, 2445-2455.
36. Petersen, N., Reimann, F., Bartfeld, S., Farin, H. F., Ringnalda, F. C., Vries, R. G. J., van den Brink, S., Clevers, H., Gribble, F. M. and de Koning, E. J. P. (2014). Generation of L cells in mouse and human small intestine organoids. Diabetes 63, 410-420.
37. Reimann, F., Habib, A. M., Tolhurst, G., Parker, H. E., Rogers, G. J. and Gribble, F. M. (2008). Glucose sensing in L cells: a primary cell study. Cell Metab. 8, 532-539.
38. Richards, S. K., Parton, L. E., Leclerc, I., Rutter, G. A. and Smith, R. M. (2005). Over-expression of AMP-activated protein kinase impairs pancreatic beta-cell function. J. Endocrinol. 187, 225-235.
39. Robinson, J., Lai, C., Martin, A., Nye, E., Tomlinson, I. and Silver, A. (2009). Oral rapamycin reduces tumour burden and vascularization in Lkb1(+/-) mice. J. Pathol. 219, 35-40.
40. Rossi, D. J., Ylikorkala, A., Korsisaari, N., Salovaara, R., Luukko, K., Launonen, V., Henkemeyer, M., Ristimaki, A., Aaltonen, L. A. and Makela, T. P. (2002). Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis. Proc. Natl. Acad. Sci. USA 99, 12327-12332.
41. Savage, A. P., Gornacz, G. E., Adrian, T. E., Ghatei, M. A., Goodlad, R. A., Wright, N. A. and Bloom, S. R. (1985). Is raised plasma peptide YY after intestinal resection in the rat responsible for the trophic response? Gut 26, 1353-1358.
42. Shackelford, D. B. and Shaw, R. J. (2009). The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563-575.
43. Shorning, B. Y., Zabkiewicz, J., McCarthy, A., Pearson, H. B., Winton, D. J., Sansom, O. J., Ashworth, A. and Clarke, A. R. (2009). Lkb1 deficiency alters goblet and paneth cell differentiation in the small intestine. PLoS ONE 4, e4264.
44. Sun, G., Tarasov, A. I., McGinty, J. A., French, P. M., McDonald, A., Leclerc, I. and Rutter, G. A. (2010). LKB1 deletion with the RIP2.Cre transgene modifies pancreatic beta-cell morphology and enhances insulin secretion in vivo. Am. J. Physiol. 298, E1261-E1273.
45. Sun, G., Reynolds, R., Leclerc, I. and Rutter, G. A. (2011). RIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis. Dis. Model. Mech. 4, 193-202.
46. Suzuki, K., Jayasena, C. N. and Bloom, S. R. (2012). Obesity and appetite control. Exp. Diabetes Res. 2012, 824305.
47. Thorel, F., Népote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S. and Herrera, P. L. (2010). Conversion of adult pancreatic alpha-cells to beta-cells after extreme betacell loss. Nature 464, 1149-1154.
48. Trapp, S. and Richards, J. E. (2013). The gut hormone glucagon-like peptide-1 produced in brain: is this physiologically relevant? Curr. Opin. Pharmacol. 13, 964-969.
49. Udd, L., Katajisto, P., Kyyrönen, M., Ristimäki, A. P. and Mäkelä, T. P. (2010). Impaired gastric gland differentiation in Peutz-Jeghers syndrome. Am. J. Pathol. 176, 2467-2476.
50. Ullman-Culleré, M. H. and Foltz, C. J. (1999). Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab. Anim. Sci. 49, 319-323.
51. Ylikorkala, A., Rossi, D. J., Korsisaari, N., Luukko, K., Alitalo, K., Henkemeyer, M. and Mäkelä, T. P. (2001). Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science 293, 1323-1326.
52. Zariwala, H. A., Borghuis, B. G., Hoogland, T. M., Madisen, L., Tian, L., De Zeeuw, C. I., Zeng, H., Looger, L. L., Svoboda, K. and Chen, T. W. (2012). A Credependent GCaMP3 reporter mouse for neuronal imaging in vivo. J. Neurosci. 32, 3131-3141.