SUFU (SUFU Negative Regulator Of Hedgehog Signaling)

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

These findings provide new structure-function insights into a key signaling complex mutated in cancer and other diseases. Summary: Alphafold3 predicts a more extended interaction of the GLI1 transcription factor with the tumor suppressor SUFU than has been seen in published x-ray structures; these predictions are supported by structure-function experiments, including analysis of patient-derived missense variants of SUFU.

As Professor Sydney Gellis remarked, 'When he gets down to the ovaries, he's gone about as far as he can go', capturing Gorlin's expansive curiosity and expertise. As well as the legacy of the syndromes he has been associated with, he has left a blueprint for all clinical colleagues to take forward in their daily practice - empathy, humour and generosity of spirit.

We showed that pantoprazole may reduce the tumorigenicity of GCSCs through the Wnt signaling pathway. Therefore, pantoprazole may be an assistance treatment for gastric cancer therapy.

This first report of familial non-WNT/non-SHH MBs highlights novel somatic (NF1) and germline (KYAT3, SPATA31A6) variants, suggesting unexplored oncogenic mechanisms. The findings underscore the need for further research to elucidate drivers of non-WNT/non-SHH MBs and develop targeted therapies. WES proves critical in uncovering genetic underpinnings of rare familial MBs.

SuFu's rare somatic mutations (~1%) had clinical value and were confirmed as markers of LUAD progression, providing new insights into the pathogenesis of LUAD. Potential therapeutic strategies involving the SuFu-Gli1 axis have also been proposed for precision medicine in the treatment of LUAD.

Rarely, this condition is related to a suppressor of fused gene mutation, which occurs downstream from Smoothened, and is unresponsive to Smoothened inhibitors including vismodegib and sonidegib. Genetic testing was negative for patched 1 and patched 2 mutations but positive for a heterozygous suppressor of fused mutation. Patients with basal cell nevus syndrome should be treated with surgical excision, counseled on sun protection, screened and monitored for complications, and treated with vismodegib (if associated with patched 1 mutation) or itraconazole (if associated with suppressor of fused mutation).

Moreover, STAT3 ablation abolished the Ssb1-mediated antifibrotic effects. These findings show that STAT3 plays a vital role in Ssb1 treatment of liver fibrosis, and Ssb1 as a STAT3 inhibitor might be a promising therapeutic candidate for the treatment of hepatic fibrosis.

By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-depending signals use distinct but interacting effects on cell behavior...Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

Both had a novel germline splice-region variant that was originally classified as a variant of uncertain significance. We used cDNA analysis to provide additional evidence to allow re-classification of the non-canonical splice variant and provide a formal genetic diagnosis that can also be used for family planning and to screen at-risk relatives.

Given the frequent involvement of the stomatognathic system in GGS, dentists play a critical role in early detection and referral. Comprehensive family-based screening is essential for timely diagnosis, improved monitoring, and effective management of this multisystem disorder.

Analysis of DNA from tumor tissue using the TWIST Exome 2.0 Panel revealed de novo pathogenic SUFU (c.183-2 A > G) and PTEN (c.389G > A) variants. This paper establishes an initial link between LDD and germline SUFU along with somatic PTEN variants identified from tumor tissue, providing novel insights into the molecular pathogenesis of this rare condition.