RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma

Lucia Di Marcotullio, Elisabetta Ferretti, Enrico De Smaele, Beatrice Argenti, Claudia Mincione, Francesca Zazzeroni, Rita Gallo, Laura Masuelli, Maddalena Napolitano, Marella Maroder, Andrea Modesti, Felice Giangaspero, Isabella Screpanti, Edoardo Alesse, Alberto Gulino

Research output: Contribution to journalArticlepeer-review

Abstract

Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse REN KCTD11, previously reported to be expressed in differentiating and low proliferating neuroblasts. Human RENKCTD11 maps to 17p13.2 and displays allelic deletion as well as significantly reduced expression in medulloblastoma. RENKCTD11 inhibits medulloblastoma cell proliferation and colony formation in vitro and suppresses xenograft tumor growth in vivo. RENKCTD11 seems to inhibit medulloblastoma growth by negatively regulating the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes, by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation. Therefore, we identify RENKCTD11 as a suppressor of Hedgehog signaling and suggest that its inactivation might lead to a deregulation of the tumor-promoting Hedgehog pathway in medulloblastoma.

Original languageEnglish
Pages (from-to)10833-10838
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number29
DOIs
Publication statusPublished - Jul 20 2004

Keywords

  • 17p deletion
  • Brain tumors
  • Gli
  • Tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • General

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