STK11 acts as a key regulator in M2 polarization through coordinating IL-4 signaling and glutamine metabolism.

PDF | Single-cell RNA sequencing (scRNA-seq) is an innovative technology that can be used to characterize transcriptome heterogeneity at the single-cell... | Find, read and cite all the research you n...

Multiple sclerosis (MS) is a chronic autoimmune disorder. Dendritic cells (DCs) represent a promising therapeutic target for restoring immune homeostasis. In this study, the CLAN platform was used to

Join Drs. Ma’n Zawati & James Tsui as they lead a thought-provoking session on the use of AI in research and innovation.

Recent developments in cancer research have illuminated crucial insights into the mechanisms that render lung adenocarcinomas resistant to immunotherapy. A study led by Parker, R.E. and colleagues has revealed that high levels of the protein PER1 are closely associated with mutations in the STK11 gene—a common occurrence in lung adenocarcinoma. This correlation not only underscores the vital relationship between molecular alterations and immunotherapy effectiveness but also proposes a potential pathway for targeted therapeutic strategies.

Welcome to This is Epigenetics!—a bilingual podcast, produced by the CEEHRC trainee committee, where we interview renowned Canadian scientists about their career, their research and, more importantly,...

Despite the development of new classes of therapeutics in oncology, patients with tumors harboring mutations in the tumor suppressor gene STK11/LKB1 continue to exhibit poor clinical response and therapeutic resistance. Recent advances in the understanding of LKB1-mutant tumor biology have illuminated how metabolism and the tumor microenvironment (TME) function as effectors of the aggressive nature of this tumor type. New findings have revealed how metabolic reprogramming, a hallmark of LKB1-mutant tumor biology, can be exploited as a potential targetable liability in these tumors. Characterization of the distinctly immunosuppressive LKB1-mutant TME has motivated multiple discoveries of new approaches for rewiring the microenvironment to overcome immunotherapy resistance. Indeed, overcoming therapeutic resistance in LKB1-deficient tumors continues to be a major research focus, and some preclinical studies have advanced to clinical trials. In this review, we critically analyze these findings and discuss therapies in development that aim to leverage this new understanding for clinical benefit.

Sun et al. report that high-dose ascorbic acid selectively induces pyroptosis in lung cancer with LKB1 deficiency via the ROS-caspase-3-GSDME axis. This promotes dendritic cell activation and progenitor-exhausted T cell expansion, ultimately sensitizing immunotherapy in LKB1-deficient lung cancer.

Galan-Cobo et al. demonstrate that KRAS-mutant non-small cell lung cancers with STK11/LKB1 and KEAP1 co-occurring alterations show a dependency on ATR-CHK1 signaling. They present preclinical and clinical data supporting the efficacy of combining the ATR inhibitor ceralasertib and the PD-L1 inhibitor durvalumab in tumors harboring these mutations, a regimen currently undergoing phase III clinical testing.

Unlock the complexities of epigenomic data analysis with this comprehensive guide, from quality control to visualization.

The accurate description and subsequent modeling of protein interactomes require quantification of their affinities at the proteome-wide scale. Here we develop and validate the Holdup Multiplex, a versatile assay with a mass spectrometry (MS) readout for profiling the affinities of a protein for large pools of peptides. The method can precisely quantify, in one single run, thousands of affinity constants over several orders of magnitude. The throughput, dynamic range, and sensitivity can be pushed to the performance limit of the MS readout. We applied the Holdup Multiplex to quantify in a few sample runs the affinities of the 14–3–3s, phosphoreader proteins highly abundant in humans, for 1000 different phosphopeptides. The seven human 14–3–3 isoforms were found to display similar specificities but staggered affinities, with 14–3–3γ being always the best binder and 14–3–3ε and σ being the weakest. Hundreds of new 14–3–3 binding sites were identified. We also identified dozens of 14–3–3 binding sites, some intervening in key signaling pathways, that were either stabilized or destabilized by the phytotoxin Fusicoccin-A. The results were corroborated by X-ray crystallography. Finally, we demonstrated the transferability of the Holdup Multiplex by quantifying the interactions of a PDZ domain for 5400 PBM peptides at once. The approach is applicable to any category of protein-binding ligands that can be quantifiable by mass spectrometry.

ILC3s are essential for intestinal defense; however, how metabolism affects their function has remained elusive. Fonseca-Pereira et al. show that LKB1 controls ILC3 function in a cell-intrinsic manner...