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Potential for use of macrocyclic peptide encompassing the L2 loop sequence from HHIP to disrupt SHH binding as a therapy.
HHIP primarily interacts with SHH via an extended loop located in the extracellular domain of HHIP. Acts as a structural decoy receptor for vertebrate Hh.
HHIP forms part of a negative feedback loop by binding to the hedgehog signaling ligands
demonstration that the systemic deletion of HHIP could have a positive effect on tumour angiogenesis.
HHIP methylated in squamous cell carcinomas of the head and neck. Corroborates with activation of Wnt signaling related to epigenetic silencing of its negative regulators (Diagnostic relevance).
HHIP found to be epigenetically silenced in lung adenocarcinomas. Overexpression of HHIP blocked HH activation - suggests silencing of HHIP is critical in potentiating HH activation and maintaining cell survival under stress conditions.
HHIP was shown to have higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1 and GLI3 were detected in these samples. (Uterine smooth muscle)
Daily treatment with Vismodegib (Hh antagonist) downregulated Hh target genes Gli1, Hhip and Ptch1 and caused significant reduction of tumour volume and tumour growth delay.
Exogeneous GPC3 treatment of HSCs decreases the mRNA expression of Hh target genes including Ptch1 and HHIP
HSulf-1 suppressed cellular proliferation and growth in gastric cancer cells. Inhibits Gli-mediated transcription and down-regulates the expression of Hedgehog target genes including GLI1, PTCH1/2, HHIP, CCND1, C-MYC, and BCC-2
Levels of Hh targets GLI1, HHIP and PTCH1 increased in SCC compared with normal tissue from the same patients (oesophagus)
HHIP, PDGFRa, SMO and SuFU gene highly expressed in primary oesophageal squamous cell tissue. Transcripts expressed in 13/15 oesphageal cancers.
HHIP methylation in 3/11 cell lines and 9/41 neuroblastoma samples.
Reduced expression of HHIP in most GI cancer cell lines and in a certain subset of cancer tissues which correlated with promoter hypermethylation. Overexpression HHIP in some with correlation between expression levels and SHH, Indian hedgehog, Patched and GLI-1
THe gene encoding the Hhip is transcriptionally silenced by CpG island promoter hypermethylation in 26% of HB cases. Treatmnet with DNA-demethylating agent partially restored HHIP expression.
HHIP, Ptch1 and Gli-1 mainly detected in malignant crypts of adenocarcinomas
Found essentially no enhanced accumulation of mRNA from PTCH1, GLI-1, HIP and PDGFRa indicating that HH dysregulation is not crucial in the development of most common non-BCC cancers. Molecular pathogenesis of BCCs differs markedly from that of most other cancers.
mRNA expression of HIP and PTC genes were enhanced in all samples of BCCs whereas none of the other skin tumours tested exhibited an increased level of such mRNA as compared with normal skin. Indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs. Also showed that HIP is linked with the expression of the PTC gene but not the SHH gene.
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