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SGK1, autophagy and cancer: an overview

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Abstract

Background

The serum and glucocorticoid-induced kinase-1 (SGK1) belonging to the AGC protein kinase family phosphorylates serine and threonine residues of target proteins. It regulates numerous ion channels and transporters and promotes survival under cellular stress. Unique to SGK1 is a tight control at transcriptional and post-transcriptional levels. SGK1 regulates multiple signal transduction pathways related to tumor development. Several studies have reported that SGK1 is upregulated in different types of human malignancies and induces resistance against inhibitors, drugs, and targeted therapies.

Results and Conclusion

This review highlights the cellular functions of SGK1, its crucial role in cancer development, and clinical insights for SGK1 targeted therapies. Furthermore, the role of SGK1-mediated autophagy as a potential therapeutic target for cancer has been discussed.

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Abbreviations

SGK:

Serum and glucocorticoid-induced kinase-1

AKT:

Protein kinase B

PKA:

CAMP dependent protein kinase

PDK1:

Phosphoinositide dependent protein kinase-1

PKG:

CGMP dependent protein kinase

S6K:

Ribosomal S6 kinase

PKC:

Protein kinase C

MAST:

Microtubule-associated serine/threonine kinase

ROCK:

Rho-associated protein kinase

YANK:

Yet another novel kinase

GRK:

G protein-coupled receptor kinase

Nt:

Amino-terminus

Ct:

Carboxy-terminus

ER:

Endoplasmic reticulum

PIP3 :

Phosphatidylinositol-trisphosphate

TGFβ:

Growth factor beta

FSH:

Follicle stimulating hormone

ENaC:

Epithelial sodium channel

Th1:

Type-1 T helper cells

Tregs:

Regulatory T cells

ECM:

Extra cellular matrix

TME:

Tumor microenvironment

mTORC1:

Mammalian target of rapamycin complex-1

YAP:

Yes-associated protein

GLI1:

GLI family zinc finger-1

MTA1:

Metastasis-associated protein-1

PIN1:

Peptidyl-prolyl cis/trans isomerase NIMA-interacting-1

TAMs:

Tumor-associated macrophages

APC:

Adenomatous polyposis coli

shRNA:

Short hairpin RNA

CMA:

Chaperone-mediated autophagy

LAMP2A:

Lysosomal-associated membrane protein-2A

LC3B2:

Microtubule-associated proteins 1A/1B light chain-3B2

FOXO3:

Forkhead box O3

ULK1:

Unc-51 like autophagy activating kinase-1

BECN1:

Beclin-1

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  1. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Haidian District, Beijing, 100084, China

    Madiha Javeed Ghani

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MJG conceptualized the study, searched the literature, drafted and reviewed the manuscript, and designed illustrations using BioRender tool.

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Ghani, M.J. SGK1, autophagy and cancer: an overview. Mol Biol Rep 49, 675–685 (2022). https://doi.org/10.1007/s11033-021-06836-6

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