LKB1 (STK11)

Single-cell RNA-seq is younger than the iPhone. 🤯 The first bona fide scRNA-seq transcriptomes were published in 2009 by Tang et al., who sequenced individual mouse cells and showed you could capture a whole transcriptome from a single cell. From “sci-fi” to standard tool in just over a decade...

From "The Tumor Suppressor Kinase LKB1: Metabolic Nexus" by Mohammed Bourouh, Paola A. Marignani. HIF1α promotes expression of glycolytic enzymes. Schematic representation of glycolysis and the pentose phosphate pathway (PPP). LKB1 phosphorylates and activates AMPK which then phosphorylates and inhibits RAPTOR, thereby inhibiting mTORC1. mTORC1 promotes HIF1α upregulation. Active HIF1α promotes expression of glycolytic enzymes (red) increasing glycolysis rate. HIF1α also promotes expression of 6PGD to shunt glucose-6-phosphate to the PPP to generate NADPH for REDOX balance and for synthesis of ribose-5-phosphate for nucleotide synthesis.

www.frontiersin.org/journals/cel...

Review: "The Tumor Suppressor Kinase LKB1: Metabolic Nexus"

LKB1 loss is associated with multiple malignancies and causes metabolic reprograming to increase glycolysis and lactate production, elevate hexosamine biosynthesis and glutamine metabolism.

Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆ - Cell Death & Disease Cell Death & Disease - Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆

www.nature.com/articles/s41...

Holloway et al. reveal that adaptor protein p11 is rapidly turned over by the proteasome and that its stability is tightly controlled through both ubiquitin-dependent and ubiquitin-independent mechanisms.

🔬New Preprint Alert 🔬 How is AMPK regulated by oxidative stress? We use functional imaging to uncover spatial regulation of AMPK activity during oxidative stress by LKB1 & CaMKK2. Combining imaging with proteomics & metabolomics, we find AMPK works to promote the cellular redox response.

A Comprehensive Mutational and Histopathological Analysis of STK11-Mutant Non-Small Cell Lung Carcinomas Despite recent advances in the understanding of genomic and immunopathologic mechanisms of lung cancer, this disease remains the leading cause of canc…

Whoopsie, malformed link.

www.sciencedirect.com/science/arti...

www.sciencedirect.com/science/arti...

Authors combined targeted NGS with STAS and LVI scoring and organ-specific metastasis profiling within a single well-defined NSCLC cohort. This design allows them to directly link #STK11 mutation subtypes with distinct clinical and metastatic phenotypes. #LKB1

The authors also show in vivo protection against IgE-mediated anaphylaxis, hinting that AMPK agonists could be a real therapeutic avenue.

What’s striking is how zingerone works. By boosting LKB1/AMPK signaling, it reins in mast cell activation at the source, lowering Ca²⁺ influx, reducing granule release, and dampening the whole allergic cascade. It’s a metabolic lever with immunological consequences.

www.mdpi.com/1467-3045/47...

Zingerone, a ginger-derived compound, activates the LKB1/AMPK pathway to block IgE/FcεRI-dependent mast cell degranulation and anaphylaxis in models. Highlights AMPK agonists as potential anti-allergic therapeutics.

This review highlights the role of #LKB1 in #Tumorigenesis and its therapeutic relevance in #Oncology, offering new insights into targeted #CancerTherapy. @westernu.bsky.social #medsky

#OpenAccess: www.sciencedirect.com/science/arti...

STK11 coordinates IL-4 signaling with metabolic reprogramming to control M2 macrophage polarization and antitumor immunity STK11 acts as a key regulator in M2 polarization through coordinating IL-4 signaling and glutamine metabolism.

STK11 coordinates IL-4 signaling with metabolic reprogramming to control M2 macrophage polarization and antitumor immunity

www.science.org/doi/10.1126/...

Single-Cell RNA Sequencing Analysis Using Fluidigm C1 Platform for Characterization of Heterogeneous Transcriptomes Single-cell RNA sequencing (scRNA-seq) is an innovative technology that can be used to characterize transcriptome heterogeneity at the single-cell resolution. The Fluidigm C1 is an automated system fo...

link.springer.com/protocol/10....

(PDF) Single-Cell RNA Sequencing Analysis Using Fluidigm C1 Platform for Characterization of Heterogeneous Transcriptomes 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...

www.researchgate.net/publication/...

👀📝

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 deliver siRNAs against CD40 and LKB1 ...
#MSchat #MS #Neurology #MultipleSclerosis #NeuroSky #MedSky

Meta analysis by Alessandro Di Federico, MD, et al: Dual CTLA-4 + PD-1/PD-L1 blockade in NSCLC yielded 5-year OS of 19.8% vs 16.3% with monotherapy

Median OS was longer in patients with PD-L1 TPS <1% & STK11 mutations

Corresponding author: Biagio Ricciuti, MD, PhD

ascopost.com/news/october...

Please repost:

What are the current costs of kit-based RNA extractions per sample? Qiagen quoted my grad student a "discount" that came to $10/sample. That seemed /way/ too high

Following on from a great site visit at @cicbiogune.bsky.social last week, for #JEM_Spotlight I would like to highlight the work of @arkaitzcarracedo.bsky.social. A really interesting study investigating the role of LKB1 in metastatic prostate cancer. Take a look here 👉 doi.org/10.1084/jem....

New research alert! Dual immune checkpoint blockade significantly improves overall survival in those with PD-L1 TPS <1% and those with an STK11 mutation. #lungcancer

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

📢 Join Drs. Ma’n Zawati & James Tsui for a dynamic workshop on the ethics & impact of AI in scientific research.
📍 Attend in Montreal, UBC, or UofT, or join via Zoom!
🗓️ Free & in person with snacks🍪
🔗 Register: https://t.co/zyPptnPTP6
#AI #Genomics #CEEHRC #ScienceEthics

High PER1 Linked to STK11 Mutation in Lung Cancer 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.

High PER1 Linked to STK11 Mutation in Lung Cancer

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…

🎙️ New episode! Dr. Paola Marignani (@pmarignani.bsky.social) founder of Canadian Women in STEM, shares her journey into cancer epigenetics & why a fulfilling career doesn’t need a traditional path—just one that sparks joy!✨
🔗 shorturl.at/2bQvl
@dalhousieu.bsky.social
#WomenInSTEM #Epigenetics

A latest study showing 'tumorigenesis as a process of loss of original cell identity and gain of neural stemness'

"Loss of Lkb1 cooperates with BrafV600E and ultraviolet radiation, increasing melanoma multiplicity and neural-like dedifferentiation"
febs.onlinelibrary.wiley.com/doi/10.1002/...

Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance 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.

Targeting LKB1/STK11-mutant cancer: distinct metabolism, microenvironment, and therapeutic resistance

High-dose ascorbic acid selectively induces pyroptosis in LKB1-deficient lung cancer and sensitizes immunotherapy 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.

Online now: High-dose ascorbic acid selectively induces pyroptosis in LKB1-deficient lung cancer and sensitizes immunotherapy

KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell 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.

KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer

📣Our new paper is out in Science Immunology.

We uncovered how stem-like and effector Tph cells play distinct roles in RA pathogenesis.

🔗https://www.science.org/doi/10.1126/sciimmunol.adt3955

Exciting illustration by @chimomonga.bsky.social depicting cells as robots and dogs🤖🐶

#RA
#Tph

For something different, check out this new blog by @aminnoorani.bsky.social!

Explore a biologist’s roadmap to epigenomic data analysis, from understanding raw data to gaining deep biological insights.

thisisepigenetics.ca...

#ThisIsEpigenetics #epigenetics #epigenomics #bioinformatics

I still can't get over how cool cells can be reaching out and interacting with one another! This depth shaded membrane marker gives us an idea of how dynamic these extensions can be! #FluorescenceFriday 🔬🧪

FlyBase needs our help! There is now a system for non-European direct donations. Hopefully an option to invoice labs comes soon, but in the mean time do what you can to save this precious resource!

money spent on alcohol by generation annually in the US graph. Boomers spend $25B, GenX spends $23.1B, Millenials spends $23.4B, and GenZ spends $3.1B

my science students collect bad graphs for me and this one made us both CACKLE because of COURSE Gen Z buys the least alcohol, the youngest of them is like 13 😅