DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS

Nature Structural and Molecular Biology

Volumn 17, Issue 6, 2010, Pages 718-725

  Lauth, Matthias ^a,b   Bergström, Åsa ^a   Shimokawa, Takashi ^a   Tostar, Ulrica ^a   Jin, Qianren ^a   Fendrich, Volker ^b   Guerra, Carmen ^c   Barbacid, Mariano ^c   Toftgrd, Rune ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

^c Centro Nacional de Investigaciones Oncológicas   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ACTIN; DUAL SPECIFICITY TYROSINE PHOSPHORYLATED AND REGULATED KINASE 1B; K RAS PROTEIN; PHOSPHOTRANSFERASE; RAS PROTEIN; SMALL INTERFERING RNA; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GLI2; TRANSCRIPTION FACTOR GLI3; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOCRINE EFFECT; CANCER CELL; CARCINOGENESIS; CELL COMPARTMENTALIZATION; CELL STRAIN 3T3; CONTROLLED STUDY; EUKARYOTIC FLAGELLUM; GENE EXPRESSION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; STROMA CELL;

ADENOCARCINOMA; ANIMALS; AUTOCRINE COMMUNICATION; BASE SEQUENCE; CILIA; DISEASE MODELS, ANIMAL; GENES, RAS; HEDGEHOG PROTEINS; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MICE; MODELS, BIOLOGICAL; MUTATION; NERVE TISSUE PROTEINS; NIH 3T3 CELLS; NUCLEAR PROTEINS; PANCREATIC NEOPLASMS; PARACRINE COMMUNICATION; PROTEIN-SERINE-THREONINE KINASES; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; RNA, MESSENGER; RNA, NEOPLASM; RNA, SMALL INTERFERING; TRANSCRIPTION FACTORS;

ERINACEIDAE;

EID: 77953284901     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1833     Document Type: Article

References (47)

1. Rubin, L.L. & de Sauvage, F.J. Targeting the Hedgehog pathway in cancer. Nat. Rev. Drug Discov. 5, 1026-1033 (2006).
2. Watkins, D.N. et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 422, 313-317 (2003).
3. Berman, D.M. et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425, 846-851 (2003).
4. Thayer, S.P. et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425, 851-856 (2003).
5. Stecca, B. et al. Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc. Natl. Acad. Sci. USA 104, 5895-5900 (2007).
6. Malumbres, M. & Barbacid, M. RAS oncogenes: the frst 30 years. Nat. Rev. Cancer 3, 459-465 (2003).
7. Hezel, A.F., Kimmelman, A.C., Stanger, B.Z., Bardeesy, N. & Depinho, R.A. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 20, 1218-1249 (2006).
8. Hingorani, S.R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469-483 (2005).
9. Feldmann, G. et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res. 67, 2187-2196 (2007).
10. Feldmann, G. et al. Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer. Gut 57, 1420-1430 (2008).
11. Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-1806 (2008).
12. Yauch, R.L. et al. A paracrine requirement for hedgehog signalling in cancer. Nature 455, 406-410 (2008).
13. Habbe, N. et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc. Natl. Acad. Sci. USA 105, 18913-18918 (2008).
14. De La O, J.P. et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc. Natl. Acad. Sci. USA 105, 18907-18912 (2008).
15. Guerra, C. et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11, 291-302 (2007).
16. Morton, J.P. et al. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc. Natl. Acad. Sci. USA 104, 5103-5108 (2007).
17. Fendrich, V. et al. Hedgehog signaling is required for effective regeneration of exocrine pancreas. Gastroenterology 135, 621-631 (2008).
18. Schubbert, S., Shannon, K. & Bollag, G. Hyperactive Ras in developmental disorders and cancer. Nat. Rev. Cancer 7, 295-308 (2007).
19. Quint, K. et al. The expression pattern of PDX-1, SHH, Patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer. Pancreatology 9, 116-126 (2009).
20. Taipale, J. et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 406, 1005-1009 (2000).
21. Chen, J.K., Taipale, J., Young, K.E., Maiti, T. & Beachy, P.A. Small molecule modulation of Smoothened activity. Proc. Natl. Acad. Sci. USA 99, 14071-14076 (2002).
22. Guerra, C. et al. Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell 4, 111-120 (2003).
23. Wakabayashi, Y., Mao, J.H., Brown, K., Girardi, M. & Balmain, A. Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature 445, 761-765 (2007).
24. Svard, J. et al. Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway. Dev. Cell 10, 187-197 (2006).
25. Haycraft, C.J. et al. Gli2 and Gli3 localize to cilia and require the intrafagellar transport protein polaris for processing and function. PLoS Genet. 1, e53 (2005).
26. Schneider, L. et al. PDGFRalphaalpha signaling is regulated through the primary cilium in fbroblasts. Curr. Biol. 15, 1861-1866 (2005).
27. Lauth, M., Bergstrom, A. & Toftgard, R. Phorbol esters inhibit the Hedgehog signalling pathway downstream of Suppressor of Fused, but upstream of Gli. Oncogene 26, 5163-5168 (2007).
28. Jin, K., Park, S., Ewton, D.Z. & Friedman, E. The survival kinase Mirk/Dyrk1B is a downstream effector of oncogenic K-ras in pancreatic cancer. Cancer Res. 67, 7247-7255 (2007).
29. Mao, J. et al. Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1. J. Biol. Chem. 277, 35156-35161 (2002).
30. Varjosalo, M. et al. Application of active and kinase-defcient kinome collection for identifcation of kinases regulating hedgehog signaling. Cell 133, 537-548 (2008).
31. Heidenblad, M. et al. Genome-wide array-based comparative genomic hybridization reveals multiple amplifcation targets and novel homozygous deletions in pancreatic carcinoma cell lines. Cancer Res. 64, 3052-3059 (2004).
32. Seeley, E.S., Carriere, C., Goetze, T., Longnecker, D.S. & Korc, M. Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res. 69, 422-430 (2009).
33. Huangfu, D. et al. Hedgehog signalling in the mouse requires intrafagellar transport proteins. Nature 426, 83-87 (2003).
34. Nolan-Stevaux, O. et al. GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev. 23, 24-36 (2009).
35. Dennler, S. et al. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo. Cancer Res. 67, 6981-6986 (2007).
36. Steg, A. et al. Hedgehog pathway expression in heterogeneous pancreatic adenocarcinoma: implications for the molecular analysis of clinically available biopsies. Diagn. Mol. Pathol. 16, 229-237 (2007).
37. Nielsen, S.K. et al. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines. Dev. Dyn. 237, 2039-2052 (2008).
38. Galvin, K.E., Ye, H., Erstad, D.J., Feddersen, R. & Wetmore, C. Gli1 induces G2/M arrest and apoptosis in hippocampal but not tumor-derived neural stem cells. Stem Cells 26, 1027-1036 (2008).
39. Lauth, M. & Toftgard, R. Non-canonical activation of GLI transcription factors: implications for targeted anti-cancer therapy. Cell Cycle 6, 2458-2463 (2007).
40. Kasai, K., Inaguma, S., Yoneyama, A., Yoshikawa, K. & Ikeda, H. SCL/TAL1 interrupting locus derepresses GLI1 from the negative control of suppressor-of-fused in pancreatic cancer cell. Cancer Res. 68, 7723-7729 (2008).
41. Ji, Z., Mei, F.C., Xie, J. & Cheng, X. Oncogenic KRAS activates hedgehog signaling pathway in pancreatic cancer cells. J. Biol. Chem. 282, 14048-14055 (2007).
42. Tian, H. et al. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc. Natl. Acad. Sci. USA 106, 4254-4259 (2009).
43. Prasad, N.B. et al. Gene expression profles in pancreatic intraepithelial neoplasia refect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res. 65, 1619-1626 (2005).
44. Lauth, M., Bergstrom, A., Shimokawa, T. & Toftgard, R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc. Natl. Acad. Sci. USA 104, 8455-8460 (2007).
45. Nakashima, H. et al. Nuclear factor-κB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer. Cancer Res. 66, 7041-7049 (2006).
46. Shimokawa, T. et al. Distinct roles of frst exon variants of the tumor-suppressor Patched1 in Hedgehog signaling. Oncogene 26, 4889-4896 (2007).
47. Ikram, M.S. et al. GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. J. Invest. Dermatol. 122, 1503-1509 (2004).