BIOM3200 Project
Category: Altro
è stato aggiornato: 3 ott 2018
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Created byFran
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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 ligandsdemonstration 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 HHIPHSulf-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-2Levels 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-1THe 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 adenocarcinomasFound 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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