Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene Review:

HHIP - hedgehog interacting protein

Homo sapiens

Synonyms: FLJ20992, FLJ90230, Hedgehog-interacting protein, HIP, UNQ5825/PRO19644

Martin, S.T. et al., Katoh, Y. et al., Wallis, D.E. et al., Sacedón, R. et al., Katoh, Y. et al., et al.

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Disease relevance of HHIP

Hedgehog signaling is frequently activated in esophageal cancer, gastric cancer and pancreatic cancer due to transcriptional upregulation of Hedgehog ligands and epigenetic silencing of HHIP1/HHIP gene, encoding the Hedgehog inhibitor [1].
Restoring the expression of HHIP in pancreatic cancer cells by 5-aza-2'-deoxycytidine led to a decrease in Gli reporter activity, consistent with downregulation of Hedgehog signaling [2].

High impact information on HHIP

Other Hh-binding proteins with modulating functions, such as Hedgehog-interacting protein (Hip) and growth arrest-specific gene-1 (Gas-1), are also expressed in human thymus [3].
These include Patched (Ptc), Smoothened (Smo), cubitus interuptus (ci)/Gli, wingless (wg/Wnt, decapentaplegic (dpp)/BMP, Hedgehog interacting protein (Hip), nodal, Smads, One-eyed pinhead (Oep), and TG-Interacting Factor (TGIF) [4].
HHIP1, HHIP2 (HHIPL1 or KIAA1822) and HHIP3 (HHIPL2 or KIAA1822L) constitute human HHIP gene family [5].
HHIP maps to chromosome 4q31.21--> q31 [6].
The Human Hedgehog interacting protein (HHIP), a negative regulator of hedgehog signaling, has been shown to be underexpressed in pancreatic cancers [2].

Biological context of HHIP

These results indicate in some pancreatic adenocarcinomas that HHIP is epigenetically inactivated by promoter methylation, and its silencing could contribute to the increased Hedgehog signaling observed in pancreatic neoplasms [2].

Anatomical context of HHIP

HHIP expression could be restored in methylated cell lines using epigenetic modifier drugs [2].

References

Hedgehog signaling pathway and gastrointestinal stem cell signaling network (Review). Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006)
Aberrant methylation of the Human Hedgehog interacting protein (HHIP) gene in pancreatic neoplasms. Martin, S.T., Sato, N., Dhara, S., Chang, R., Hustinx, S.R., Abe, T., Maitra, A., Goggins, M. Cancer Biol. Ther. (2005)
Expression of hedgehog proteins in the human thymus. Sacedón, R., Varas, A., Hernández-López, C., Gutiérrez-deFrías, C., Crompton, T., Zapata, A.G., Vicente, A. J. Histochem. Cytochem. (2003)
Molecular mechanisms of holoprosencephaly. Wallis, D.E., Muenke, M. Mol. Genet. Metab. (1999)
Comparative genomics on HHIP family orthologs. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006)
The human hedgehog-interacting protein gene: structure and chromosome mapping to 4q31.21-->q31.3. Bak, M., Hansen, C., Friis Henriksen, K., Tommerup, N. Cytogenet. Cell Genet. (2001)

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