We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder.
Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease.
Molecular analysis of STRA6 was undertaken in two human fetuses from consanguineous families we previously described with Matthew-Wood syndrome in a context of severe microphthalmia, pulmonary agenesis, bilateral diaphragmatic eventration, duodenal stenosis, pancreatic malformations, and intrauterine growth retardation.
Recessive mutations in STRA6, encoding a membrane receptor for the retinol-binding protein, have been identified in some cases with PDAC syndrome, although many cases have remained unexplained.
Recessive stimulated by retinoic acid gene 6 homolog (STRA6) mutations have recently been identified as the cause of cases of PDAC in which distinct, "bushy" eyebrows have been observed.
We performed STRA6 molecular analysis in three fetuses and one child diagnosed with Matthew-Wood syndrome and in three siblings where two adult living brothers are affected with combinations of clinical anophthalmia, tetralogy of Fallot, and mental retardation.
Moreover, immunohistochemistry staining of consecutive sections demonstrated colocalization between HIF-1α and fascin in PDAC specimens, suggesting that hypoxia and HIF-1α were responsible for fascin overexpression in PDAC.
In this study, we demonstrated that BAG3 downregulation decreased IL6 release by PDACs, and IL6 reduction was, at least partially, responsible for suppression of PSCs activation by PDACs with BAG3 downmodulation.
CM from PDAC attracted and polarized THP-1 monocytes to tumor-driven like macrophages. mRNA expression cytokine profiling and ELISA identified the IL-8 secretion was increasing in tumor-driven like macrophages, and STAT3 pathway was involved.
The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway.
Moreover, PD-0332991 enhanced invasion in TGF-β-responsive PDAC cell lines that harbor a wild-type SMAD4 gene (COLO-357, PANC-1), but not in TGF-β-resistant AsPC-1 cells that harbor a mutated SMAD4.
Although ZEB1 regulates expression of S100 family members, these effects are masked by IL-6/11-STAT3 signalling, and S100 proteins cannot be considered as bona fide EMT markers in PDAC.
Taken together, our findings demonstrated that TGF-β1-induced Kindlin-2 expression promotes PDAC progression by downregulation of HOXB9 and E-cadherin.