SMURF1 (SMAD Specific E3 Ubiquitin Protein Ligase 1)

Our findings thus underscore the pivotal role of the USP29 and SMURF1 in regulating GC chemoresistance via FSP1-mediated ferroptosis suppression. FSP1 inhibition may represent a promising therapeutic avenue to overcome chemoresistance in GC.

Finally, FUT8 levels in human HCC specimens are positively correlated with CD47 expressions and negatively correlated with the infiltration of CD103+ DC and NK cells. Collectively, this study reveals a mechanism underlying CD47 upregulation in tumor cells and highlights the potential of targeting the FUT8-SMURF1-CD47 axis as a therapeutic strategy to improve anti-tumor immune responses.

Importantly, IWR-1, a specific inhibitor of the Wnt pathway, effectively inhibited Smurf1-induced GC cell proliferation and invasion. These data suggest that upregulated Smurf1 facilitates GC progression through degrading Axin2 and activating Wnt/β-catenin signaling.

INHBA promotes gemcitabine resistance in PC by stabilizing CTPS1 and enhancing pyrimidine metabolism, making it a potential target for chemosensitization in PC.

Notably, TALDO1 deacetylation inhibited its nuclear translocation and interaction with BRCA1, thereby reducing the inhibition of c-Myc transcriptional activation, promoting the expression of HK2/LDHA/PDK1, and further enhancing glycolysis independent of TALDO1 enzyme activity. This research elucidated the regulatory mechanism of TALDO1 from the perspective of acetylation modification, clarified the moonlighting functions of TALDO1 in metabolic reprogramming, and provided novel biomarkers and intervention strategies, such as HDAC inhibitors, for the clinical treatment of NPC.

These findings indicate that Gal3-CaN-Smurf1 complex interconnects with the FLCN-FNIPs to orchestrate TFEB localization and activity in response to lysosomal damage stress. Understanding Smurf1's regulation in the mTOR-TFEB axis, which balances tumor growth and stress-induced cell homeostasis, may provide novel therapeutic targets for tumor progression and drug resistance.

We extrapolate these results into a pan-cancer analysis to demonstrate that the association between SMURF1 amplification versus expression is strongest in PDAC among 23 other cancer types. Taken together, these data provide a detailed overview of the copy number landscape in PDAC while highlighting chr7q21/22 amplification as a recurrent somatic event impacting both gene expression and patient survival.

Reducing SMURF1, using a RIPK3 mutant defective in SMURF1-mediated ubiquitination, or overexpressing USP5 enhances necroptosis in leukaemia cells, leading to reduced tumour growth in xenograft models treated with birinapant and emricasan. These findings highlight the opposing regulation of K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.

This study reveals a novel oncogenic axis, where SMURF1 promotes gastric cancer progression by targeting GSTM2 for degradation. Inhibiting SMURF1 stabilizes GSTM2, leading to reduced cell proliferation, migration, and invasion both in vitro and in vivo.

The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 41: 668‑676, 2019; DOI: 10.3892/or.2018.6836].

BMP6 upregulation induces gastric cancer cell ferroptosis and sensitizes cells to doxorubicin therapy. Our findings provide a therapeutic strategy in gastric cancer.

From a therapeutic perspective, glycolysis inhibitors helped LTβR balance the proportion of Th17/Treg cells in PDOX model to inhibit tumor growth. In conclusion, our findings indicated that LTβR N-glycosylation prevented RORC ubiquitination and Foxp3 transcription, raising the Th17/Treg cell ratio and hindering HCC progression.