Serum- and Glucocorticoid-Induced Kinase Signaling in Cancer Biology

Serum- and glucocorticoid-induced kinases (SGKs) are a family of serine/threonine kinases regulated by growth factors, stress stimuli and hormonal signals. SGK1, the most studied isoform, is activated downstream of phosphoinositide 3-kinase (PI3K) via 3-phosphoinositide-dependent kinase 1 (PDK1) and mechanistic target of rapamycin (mTOR) complexes. Once activated, SGK1 phosphorylates diverse substrates that control cell survival, proliferation, ion transport, metabolic adaptation and motility. In cancer, aberrant SGK1 activity has been linked to tumour initiation, progression, metastasis and therapy resistance through modulation of apoptosis, autophagy, epithelial–mesenchymal transition (EMT) and the tumour microenvironment. SGK1 signalling overlaps extensively with the AKT pathway but can act independently to sustain oncogenic processes when AKT is inhibited. Its influence on transcription factors, cell-cycle regulators and epigenomic machinery positions SGK1 as both a biomarker and a candidate for targeted therapeutic intervention.

Research from Nature Portfolio

Recent studies have uncovered a novel mechanism by which SGK1 influences the epigenomic landscape of cancer cells. Fluctuations in SGK1 levels were shown to modulate the RAN–RANBP1–RANGAP1 axis via the SP1 transcription factor, altering the nucleo-cytoplasmic transport of precursor microRNAs. This reprogrammes miRNA maturation and downstream gene expression networks, thereby affecting tumour cell proliferation and fate decisions in both in vitro and in vivo models.

Serum- and Glucocorticoid-Induced Kinase Signaling in Cancer Biology publication trend

The graph below shows the total number of articles in serum- and glucocorticoid-induced kinase signaling in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Serine/threonine kinase: An enzyme that phosphorylates target proteins on serine or threonine residues to regulate cellular functions.

PI3K–PDK1–mTOR pathway: A signalling cascade that activates AGC kinases, including SGK and AKT, in response to growth factors.

Autophagy: A cellular self-digestion process that degrades and recycles cytoplasmic components under stress conditions.

Epithelial–mesenchymal transition (EMT): A programme by which epithelial cells acquire mesenchymal characteristics, enhancing migratory and invasive capabilities.

miRNA maturation: The processing of precursor microRNAs into mature regulatory RNAs that modulate gene expression post-transcriptionally.

References

1. SGK1 in Human Cancer: Emerging Roles and Mechanisms. Frontiers in Oncology (2021).
2. SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT. Journal of Experimental & Clinical Cancer Research (2018).
3. Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors. Biochemical Journal (2013).
4. Therapeutic inhibition of SGK1 suppresses colorectal cancer. Experimental & Molecular Medicine (2017).
5. SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation. Scientific Reports (2017).