LGR5 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 5)

Pharmacologic interventions using rapamycin and Jagged-1 further validated that Gln modulates the mTOR/Notch1 signaling cascade, leading to increased MUC2 expression and improved mucosal integrity. Collectively, these results demonstrate that Gln confers robust protection against RIII by regulating the mTOR/Notch1 axis, alleviating Notch1 overactivation, and promoting GC differentiation. These findings provide valuable mechanistic insight and experimental support for Gln as a potential therapeutic agent to prevent or mitigate radiation-induced intestinal injury.

Multicellular spheroids were separately transfected with siRNA, EXO-siRNA and, treated with cisplatin alone...However, the reduction of LGR5 expression via siRNA led to a marked decrease in SOX9 and OCT4 levels, while NANOG expression remained largely unchanged. In summary, the results indicated that LGR5 suppression is effective in reducing stemness-related genes and may be considered a good candidate for combination therapy along with chemotherapy.

The possible mechanism of NIN on UC could be explained starting from the inflammation-cancer transformation. Furthermore, comprehensive research is expected between inflammation and cancer development.

LGR5 and TFF2 are promising biomarkers for high-risk CAG identification. Their inverse expression reflects GSC dysregulation via Wnt/β-catenin signaling, offering mechanistic insights for early intervention.

This review discusses current research on dosing regimens and combination strategies involving checkpoint inhibitors, chemotherapy, and radiotherapy, as well as responses across histological subtypes. Drawing from ongoing early-phase trials and innovative approaches like CRISPR editing and dual-targeting, we highlight the progress and challenges in developing CAR-based therapies, underscoring their potential while emphasizing the need for further research to establish clinical efficacy in OC.

To investigate IL-17RA's functional role, CRC cells with stable IL-17RA overexpression were analyzed for changes in CSC marker expression, sphere formation, and 5-fluorouracil (5-FU) resistance...Specific inhibitors of IL-17RA signaling, such as the STAT3 inhibitor Stattic, reduced the expression of CD133, LGR5, ALDHA1, SOX2 and c-MYC, as well as tumor sphere formation in SW620 cells. These findings elucidate a novel IL-17RA-STAT3 axis that regulates CSC properties in CRC and highlight IL-17RA as a promising prognostic biomarker and therapeutic target for CRC treatment.

YTHDF1 promoted resistance to oxaliplatin and 5-fluorouracil in CSCs by inhibiting apoptosis and DNA damage. In conclusion, YTHDF1 promotes stemness and chemoresistance in CRC via NOTCH1 activation. Targeting YTHDF1 is a promising strategy to improve the outcome of chemotherapy in CRC.

In the present study, we demonstrate that ssRNA within fecal extracellular vesicles (FEVs) derived from bacteria, particularly those susceptible to lysis by ursodeoxycholic acid (UDCA), can suppress CRC progression via Piezo1 activation...Notably, oral UDCA administration enhanced FEV rupture, increasing luminal "naked" ssRNA and mitigating high-fat diet-induced CRC in vivo. These findings identify the bacterial ssRNA-Piezo1 axis as a potential therapeutic target in CRC.

The LGR5 expression at the invasion front was not significantly associated with either OS or RFS. The present findings suggest that LGR5 expression is associated with aggressive HCC characteristics and increased risk of recurrence, highlighting its potential as a prognostic marker for RFS in high-grade HCC.

The expression of LGR5, BMI1, CDKN1B, and YAP/TAZ was comparable in untreated and CRT rectal cancer. The uniform expression of mesenchymal niche factors might prevent the zonation of the stem cell niche in rectal cancer.

Screening of SAG1.3 derivatives identified compound 11 that competed with BODIPY-cyclopamine binding at different FZDs and inhibited WNT-induced FZD dynamics and β-catenin signaling in HEK293 cells. Furthermore, compound 11 blocked WNT-3A-induced Lgr5 gene expression in human primary hepatocyte spheroids and reduced the viability of RNF43-mutated but not RNF43-wildtype pancreatic cancer cells. Based on our data, we suggest that compound 11 acts on FZDs to limit WNT- and WNT-surrogate-induced receptor dynamics providing a valid proof-of-concept for targeting FZDs with small molecule compounds.

CRC cells infiltrating the interstitial stroma show upregulation of this fetal-like transcriptional program, which correlates with the ability of Lgr5-negative cells to initiate metastasis formation. Our findings indicate that mechanical interactions with collagen I regulate cell fate transitions associated with the metastatic cascade of CRC.