Identifiers
sonic hedgehog
HUGO:SHH hgnc_id:HGNC:10848 HGNC:10848 ENTREZ:6469 UNIPROT:Q15465
HUGO:SHH HGNC:10848 ENTREZ:6469 UNIPROT:Q15465
Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / GROWTH_FACTORS_SIGNALING_PATHWAYS
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DEPENDANCE_RECEPTORS
References
CASCADE:HH
PMID:18754008
CAFs respond to Hh stimulation by increasing the production of ECM.
Stromal hedgehog signalling can support tumour growth.
subsets of colorectal, endometrial, ovarian and pancreatic cancers overexpressed Hh ligand mRNA (data not shown). Quantitative polymerase chain reaction with reverse transcription (RT???PCR) profiling of an independent set of human tissue specimens confirmed that the transcript levels of SHH and/or Indian hedgehog homologue (IHH) ligands were significantly upregulated in subsets of these cancers.
PMID:24856585
Sonic hedgehog (Shh), a soluble ligand overexpressed by neoplastic cells in pancreatic ductal adenocarcinoma (PDAC), drives formation of a fibroblast-rich desmoplastic stroma.
Shh-deficient tumors had reduced stromal content. Surprisingly, such tumors were more aggressive and exhibited undifferentiated histology, increased vascularity, and heightened proliferation--features that were fully recapitulated in control mice treated with a Smoothened inhibitor. Furthermore, administration of VEGFR blocking antibody selectively improved survival of Shh-deficient tumors, indicating that Hedgehog-driven stroma suppresses tumor growth in part by restraining tumor angiogenesis. Together, these data demonstrate that some components of the tumor stroma can act to restrain tumor growth.
Shh deletion results in greater vascular density and proliferation within pancreatic tumors
PMID:22354771
SHH stimulates the release of ECM and induces fibrosis.
SHH significantly increased the mRNA levels of COL1A1 and COL1A2
Myofibroblasts can be identified by the expression of ??-SMA and the formation of stress fibers. Stimulation with SHH increased the protein levels of ??-SMA in resting dermal fibroblasts in a dose-dependent manner, to a mean ?? SEM of 807 ?? 327% (P = 0.007) (Figures 5A and B). Consistent with the induction of ??-SMA, SHH induced the formation of stress fibers in resting fibroblasts
PMID:20495383
In the absence of SHH; Patched recruits a dral-tucan complex that lead to apoptosis
Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DEPENDANCE_RECEPTORS
References
rc_re1703( Regulated Cell Death ):
PMID:20495383
In the absence of SHH; Patched recruits a dral-tucan complex that lead to apoptosis
SHH@Extracellular space + PTCH*@Cytosol