ArticleOncogene2020
Serum- and glucocorticoid- inducible kinase 2, SGK2, is a novel autophagy regulator and modulates platinum drugs response in cancer cells.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- SGK1 inhibition supports neuroprotection in spinal cord injury by suppressing oxidative stress and AIM2 activation via FoxO1 mediated mitophagy.Journal of neuroinflammation · 2026Article
- SGK2 mediates apoptosis in herpes simplex keratitis by suppressing protective autophagy via the mTOR pathway.Virology journal · 2026Article
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Identification of cancer mini-drivers by deciphering selective landscape in the cancer genome.Briefings in bioinformatics · 2026Article
- Death-ision: the link between cellular resilience and cancer resistance to treatments.Molecular cancer · 2025Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- AGC kinase inhibitors regulate STING signaling through SGK-dependent and SGK-independent mechanisms.Cell chemical biology · 2023Article
- SGK2 promotes prostate cancer metastasis by inhibiting ferroptosis via upregulating GPX4.Cell death & disease · 2023Article
- Glucocorticoid-induced microRNA-378 signaling mediates the progression of pancreatic cancer by enhancing autophagy.Cell death & disease · 2022Article
- Is Autophagy Always a Barrier to Cisplatin Therapy?Biomolecules · 2022Review
- A human kinase yeast array for the identification of kinases modulating phosphorylation-dependent protein-protein interactions.Molecular systems biology · 2022Article
- SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1.Molecular cancer research : MCR · 2022Article
- Progression Risk Score Estimation Based on Immunostaining Data in Oral Cancer Using Unsupervised Hierarchical Clustering Analysis: A Retrospective Study in Taiwan.Journal of personalized medicine · 2021Article
- How the glucocorticoid receptor contributes to platinum-based therapy resistance in solid cancer.Nature communications · 2021Article
- Protein Kinase SGK2 Is Induced by the βFrontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For many tumor types chemotherapy still represents the therapy of choice and many standard treatments are based on the use of platinum (PT) drugs. However, de novo or acquired resistance to platinum is frequent and leads to disease progression. In Epithelial Ovarian Cancer (EOC) patients, PT-resistant recurrences are very common and improving the response to treatment still represents an unmet clinical need. To identify new modulators of PT-sensitivity, we performed a loss-of-function screening targeting 680 genes potentially involved in the response of EOC cells to platinum. We found that SGK2 (Serum-and Glucocorticoid-inducible kinase 2) plays a key role in PT-response. We show here that EOC cells relay on the induction of autophagy to escape PT-induced death and that SGK2 inhibition increases PT sensitivity inducing a block in the autophagy cascade due to the impairment of lysosomal acidification. Mechanistically we demonstrate that SGK2 controls autophagy in a kinase-dependent manner by binding and inhibiting the V-ATPase proton pump. Accordingly, SGK2 phosphorylates the subunit V1H (ATP6V1H) of V-ATPase and silencing or chemical inhibition of SGK2, affects the normal autophagic flux and sensitizes EOC cells to platinum. Hence, we identified a new pathway that links autophagy to the survival of cancer cells under platinum treatment in which the druggable kinase SGK2 plays a central role. Our data suggest that blocking autophagy via SGK2 inhibition could represent a novel therapeutic strategy to improve patients' response to platinum.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.