LKB1: THE STAR OF THE SHOW

July 2, 2021

Endothelial Cell-Specific LKB1 Deletion Causes Endothelial Dysfunction and Hypertension in Mice in vivo.

The gene, also known as STK11, is involved in controlling blood sugar levels. 

LKB1 programs the metabolic and functional fitness of Treg cells in the control of immune tolerance and homeostasis. Mice with a Treg-specific deletion of LKB1 developed a fatal inflammatory disease characterized by excessive TH2-type-dominant responses. LKB1 deficiency disrupted Treg cell survival and mitochondrial fitness and metabolism, but also induced aberrant expression of immune regulatory molecules including the negative co-receptor PD-1 and the TNF receptor superfamily proteins GITR and OX40. The results point to functional exhaustion of Treg cells as a possible culprit in the immune response associated with allergic reaction, known as the Th2 response. “The research suggests a possible new therapeutic approach to autoimmune disorders that would be designed to boost the function of regulatory T cells by modulating  cell metabolism," Chi said.

Additionally, LKB1 inactivation modulates chromatin accessibility to drive metastatic progression of cancer. Loss of LKB1 activates the early endoderm transcription factor SOX17 in metastases and a metastatic-like sub-population of cancer cells within primary tumors. SOX17 expression is necessary and sufficient to drive a second wave of epigenetic changes in LKB1-deficient cells that enhances metastatic ability. Overall, our study demonstrates how the downstream effects of an individual driver mutation can appear to change throughout cancer development, with implications for stage-specific therapeutic resistance mechanisms and the gene regulatory underpinnings of metastatic evolution.

Is SARS-CoV-2 downregulating LKB1? Is it causing the development of autoantibodies against LKB1?  Also, does anyone know anything about this project? I can’t find anything: The project titled “Elucidation of Serine Threonine Kinase 11 Interacting Protein as a Predictor for SARS-CoV-2 Infection using a Rotavirus Model,” is being led by Crystal Boudreaux, Ph.D., assistant  professor of microbiology in West Virginia School of Osteopathic Medicine’s Department of Biomedical Sciences. 

Referenced/Related Papers

Homeostatic control of metabolic and functional fitness of Treg cells by LKB1 signalling

https://www.nature.com/articles/nature23665

LKB1 inactivation modulates chromatin accessibility to drive metastatic progression

https://www.biorxiv.org/content/10.1101/2021.03.29.437560v1

The tumor suppressor kinase LKB1: lessons from mouse models

https://academic.oup.com/jmcb/article/3/6/330/881793

Gene Variation Predicts Response To Treatment In Common Infertility Disorder, Study Shows

https://www.sciencedaily.com/releases/2008/03/080330184817.htm