STK11 expression

The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4+ T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.

Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology. Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling.

LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted.

In this series, LKB1 expression was negatively associated with the presence of CD8+ TILs. Future studies will evaluate pts treated with chemoimmunotherapy and expand TIME analysis.

Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.

Finally, in DU145 cells lacking the LKB1 gene, exogenously induced LKB1 expression restored AMPK phosphorylation by auraptene, indicating the essential role of LKB1. In summary, auraptene is a potent AMPK activator that acts by elevating the AMP/ATP ratio, thereby potentially suppressing prostate cancer progression, via at least three molecular mechanisms, including suppression of the mTOR-S6K pathway, reduced lipid synthesis, and AR downregulation caused by AMPK activation.

Our analysis demonstrated significantly lower PD-L1 expression in NSCLC patients with BrMet and STK11m compared to STK11wt. STK11m demonstrated a poor correlation with PD-L1 and TMB. This association may impact response to therapy and prognosis in patients with STK11m.

The complement pathway is a central part of the innate immune system and emerging data have identified local tumor induced complement pathway effector generation as distinct from peripheral complement components. Tumor produced complement factors can modulate tumor signaling and the TME promoting tumor growth and immune evasion. Our study implicates the complement pathway as a potential therapeutic target in STK11 mutant NSCLC with the growth of Stk11-KO tumors dependent on tumor-derived C3 suppressing T-cell immunity and these effects potentially mediated through the recruitment of PMN in the TME through the Cxcr2 signaling axis.

Alteration of STK11 mutational or mRNA/protein status might be used as a potential predictive biomarker for the prognosis of the clinical outcomes in CCA patients.

In conclusion, LKB1 expression is related to tumor size, differentiation, depth of invasion, lymph node metastasis, and TNM stage, and low LKB1 expression can predict a poor prognosis. LKB1 is a potentially valuable prognosis signature and therapeutic target in GC patients.

Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P<0.0001) and perforin (P=0.0042) from CD8+T cells, thereby impairing their cytotoxicity and promoting tumor growth. Our data suggest that LKB1 can enhance DC-mediated T cell immunity by restraining Treg development and thereby suppressing tumor growth.

STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.

Thus, LKB1 sustains mammary epithelial morphogenesis by limiting pathways that promote EMT. The observed downregulation of LKB1 expression in breast cancer is therefore predicted to associate with enhanced EMT induced by SNAI1 and TGFβ family members.

Moreover, GC patients with low LKB1 expression had a poor objective response rate, and worse progression-free survival and overall survival when treated with pembrolizumab. In conclusion, LKB1 may be a potential immune checkpoint in GC patients.

In addition, the expression of β-catenin, COX-2, and HMGB1 were upregulated, as well as the expression of p16 was downregulated. These findings suggest that changes in the AMPK signaling pathway exacerbate the deterioration of disrupted energy metabolism, chronic inflammation, hypoxia, and cellular aging in the tumor microenvironment, promoting the development of fatty liver into liver cancer.

(4) Patients with an LKB1 loss had worse clinical outcomes. This study warrants prospective assessments to confirm the prognostic role of the LKB1 expression in advanced NSCLC.

This study revealed the mechanism of STK11 mutation regulating NK cytotoxicity and promoting tumor development, providing scientific basis for the exploration of STK11-related LUAD therapeutic targets and theoretical reference for developing new NK cell-based immunotherapy.

These findings confirmed that Lkb1-regulated Tregs are critical for immune escape in DLBCL, which emphasizes that Lkb1 is a potential target for the immunotherapy of DLBCL.

We recently unveiled the vulnerability of KRAS/LKB1 co-mutated (KL) patient-derived xenografts (PDXs) to metabolic stress-based treatments, and a clinical trial to test the efficacy of metformin and fasting-mimicking diet on KL NSCLC is currently ongoing in our Institute... We validated miR-17 as epigenetic regulator of LKB1 expression in NSCLC tumors. We propose a miR-17 expression score potentially exploitable to discriminate LKB1WT NSCLC patients with impaired LKB1 expression and poor outcome, eligible for energy-stress-based treatments.

This results in reversal of EMT genes and diminished capabilities to form spheres. Future studies will be dedicated to identifying which of the 14 downstream kinases LKB1 activates to exert its functions.

We screened a panel of KRAS-mutant NSCLC cell lines as well as patient-derived xenograft (PDX) mouse models and observed that loss of the tumor suppressor STK11/LKB1 is associated with increased sensitivity to combined MAPK (either the KRAS G12C inhibitor sotorasib or MEK inhibitor trametinib) and MCL-1 inhibition (AMG 176). Consistent with this mechanism, ex vivo treatment of tumor tissue from a KRAS-LKB1 mutant NSCLC patient with sotorasib or trametinib increased MCL-1 dependent priming. These results reveal a novel link between LKB1 and the regulation of BCL-2 family proteins and provide preclinical rationale for evaluation of combined KRAS G12C + MCL-1 inhibitors for KRAS-LKB1 mutant NSCLC.

Altogether, our results showed that capsaicin affected AMPK activity in an LKB1- and TRPV1-dependent fashion, linking TRPV1 with cell fate. These data also suggest that capsaicin may be a rational chemotherapeutic option for prostate tumors.

These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.

The LKB1 gene may be associated with benign transformations rather than the tumors in prostate pathogenesis when its expression and mutation status are considered. However, the mechanism of LKB1 in PCa needs further studies.

No abstract available

Treatment with the clinically used drug metformin impaired 3D-gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D-gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.

Moreover, knocking down PRMT5 could weaken the tumor growth and lung metastasis in vivo with upregulating the LKB1 expression and the p-AMPK level and downregulating the p-mTOR expression. PRMT5 may act as a tumor-inducing agent in ESCC by modulating LKB1/AMPK/mTOR pathway signaling.

The above findings were confirmed in clinical KRAS-mutated lung cancer patients. We conclude that loss of LKB1 promotes ALKBH5 transcription by a DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer.

STK11 may play a canonical role in malignant progression and poor survival of patients with IPMNs. Aberrant STK11-driven phosphorylated AMPK downregulation may provide therapeutic opportunities with mTOR inhibitors/AMPK activators.

We identified miR-17 as a mediator of LKB1 expression in NSCLC tumors. This study proposes a miR-17 expression score potentially exploitable to discriminate LKB1 NSCLC patients with impaired LKB1 expression and poor outcome, eligible for energy-stress based treatments.

Moreover, STK11neg/Gal-3high signature had a relevant impact on CD4+, CD8+ and NK number and LDH levels.Conclusions STK11neg and Gal-3high may represent a poor prognostic trait in ICI-treated NSCLC patients. The correlation of STK11 and Galectin with circulating factors underlies a close interplay between tissue and peripheral blood compartments, ultimately featuring the tumor-host interaction and the proneness to respond to ICIs

No significant association was found between LKB1 and TIME; pAMPK was significantly associated with absent PD-L1 expression on TC (p = 0.040) and TIIC (p = 0.016).Conclusions LKB1/pAMPK deregulation may be associated with metastatic stage and lack of LKB1 expression warrants further validation as poor prognostic marker. Studies on a validation cohort of metastatic SCLC are ongoing while DNA genotyping of LKB1 is planned in LD

Transcriptome analysis showed a significant downregulation of proteins associated with apoptosis in the specimens with STK11 loss. STK11 loss may have triggered the rapid progression of PTTM from a comprehensive genomic analysis.

Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFR and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFR.

P2, N=64, Recruiting, Marina Garassino | Not yet recruiting --> Recruiting

Low LKB1/STK11 expression is associated with specific patient characteristics and poor postoperative prognosis in chemotherapy-naïve lung adenocarcinoma. Further investigation is warranted to delineate its clinical significance in the context of evaluating novel therapeutic agents in patients with resectable disease.

This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia.

STK11/LKB1 expression, as measured by immunohistochemistry, could be a useful biomarker associated with the efficacy of pembrolizumab monotherapy for patients with NSCLC and a TPS ≥50%.

Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR/LKB1/p-AMPK/PDK4/p-CREB/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.

Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.