Hedgehog Signaling in Development and Cancer

Jen, Jin; Hui, Chi Chung

doi:10.1016/j.devcel.2008.11.010

Cited by 980 publications

(1,023 citation statements)

References 146 publications

(216 reference statements)

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“…The Notch and Hedgehog signaling pathways are closely related to the Wnt/b-catenin pathway, with many components in common. 29,30 One novel finding of this study is activation of the androgen receptor signaling pathway in solid-pseudopapillary neoplasm. We have demonstrated increased androgen receptor expression at the transcriptional and translational levels.…”

Section: Discussionmentioning

confidence: 88%

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

et al. 2014

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Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/b-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of b-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transitionrelated markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.

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Section: Discussionmentioning

confidence: 88%

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

et al. 2014

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“…In the absence of soluble Hh ligands, the surface membrane molecule Patched blocks Smo (Smoothened) activity in the cell membrane and cytosolic full-length Gli proteins are proteolytically processed to generate truncated forms that act as transcriptional repressors of Hh target genes. When Hh is present, Patched block on Smo is released and Gli proteins remain in their full-length, activated state to empower Hh-dependent transcription (reviewed in Jiang and Hui 19 ). The Hh is also a crucial signaling pathway involved in the formation and maintenance of adult HSC (reviewed in Mar et al 20 ).…”

Section: A Possible Role For Ck2 In Hematopoiesis?mentioning

confidence: 99%

Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways

et al. 2012

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CK2 is a multitask kinase whose role is essential for a countless number of cellular processes, many of which are critical for blood cell development. A prevailing task for this kinase rests on counteracting programmed cell death triggered by multiple stimuli. CK2 is overexpressed in many solid tumors and in vivo mouse models have proven its tumorigenic potential. Recent data have suggested that CK2 may also have a significant role in the pathogenesis of hematopoietic tumors, such as multiple myeloma, chronic lymphocytic leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia and chronic myeloproliferative neoplasms. CK2 regulates hematopoiesis-associated signaling pathways and seems to reinforce biochemical cascades indispensable for tumor growth, proliferation and resistance to conventional and novel cytotoxic agents. Although its activity is multifold, recent evidence supports the rationale of CK2 inhibition as a therapeutic strategy in solid and hematological tumors and phase-I clinical trials are in progress to test the efficacy of this innovative therapeutic approach. In this review, we will summarize the data supporting CK2 as an oncogenic kinase in blood tumors and we will describe some critical signaling pathways, whose regulation by this protein kinase may be implicated in tumorigenesis. Leukemia (2012Leukemia ( ) 26, 1174Leukemia ( --1179 doi:10.1038/leu.2011; published online 13 January 2012Keywords: hematopoiesis; blood tumors; protein kinase CK2; kinase inhibitors INTRODUCTION Protein kinase CK2 is a highly conserved pleiotropic acidophilic serine-threonine kinase whose essential role in several cellular processes has been increasingly appreciated over the last decade. 1 Structurally, CK2 is a tetrameric enzyme, composed by the assembly of two catalytic (a and/or a') and two regulatory b subunits. The catalytic and regulatory subunits may also be present in the cell as unassembled molecules and it seems that this state is associated with distinct and specific functions. The two catalytic subunits a and a' share 90% sequence homology in their N-terminal region. The regulatory subunit b instead does not have any similarity to the other two subunits. 2 CK2 recognizes motifs characterized by a S/T N-terminal to acidic amino acids, its minimum consensus being S/T-X-X-Ac, where X is any amino acid and Ac is a residue with a carboxylic or phosphorylated side chain (E, D, pS, pY).The spectrum of actions of this kinase is impressive as it can phosphorylate hundreds of substrate proteins, which are involved in disparate cellular processes, such as regulation of cell structure, division, proliferation, programmed death, DNA damage repair, protein translation, gene transcription, organelle function and so forth. 3 It has been estimated that a substantial proportion of the human phosphoproteome (up to 20%) is generated by CK2 alone. For this reason, CK2 has long been viewed as a 'non-targetable' kinase for therapeutic purposes.The essential role of CK2 for cell and organism life is underscored by th...

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“…As an essential developmental signaling pathway, the Hh pathway is critical for maintaining tissue polarity and stem cell population. Inactivation of this pathway causes developmental defects such as holoprosencephaly (Bale, 2002), whereas hyperactivation of this pathway is found in most basal cell carcinomas (BCCs) and many extracutaneous cancers (Xie, 2005;Epstein, 2008;Jiang and Hui, 2008;Xie, 2008a, c). The emerging role of Hh signaling in human cancer further emphasizes the relevance of studying this pathway to human health.…”

Section: Introductionmentioning

confidence: 99%

Activation of the hedgehog-signaling pathway in human cancer and the clinical implications

et al. 2009

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Hedgehog Signaling in Development and Cancer

Cited by 980 publications

References 146 publications

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

Protein kinase CK2 in hematologic malignancies: reliance on a pivotal cell survival regulator by oncogenic signaling pathways

Activation of the hedgehog-signaling pathway in human cancer and the clinical implications

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