Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients

Zhang, Junjia; Miki, Yasuhiro; Iwabuchi, Erina; Xu, Jia; Kanai, Ayako; Sagara, Yasuaki; Ohi, Yasuyo; Rai, Yoshiaki; Yamaguchi, Rin; Tanaka, Maki; Ishida, Toru; Suzuki, Takashi; Sasano, Hironobu

doi:10.1007/s10549-023-06990-4

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…GR activation also acts via the induction of serum- and glucocorticoid-induced kinase-1 (SGK1) upregulation, which is a significant contributor to many cancers, including triple-negative breast cancer (TNBC), where it contributes to GR potentiation of metastasis and proliferation [ 66 ]. SGK1 is variably regulated by numerous transcription factors and epigenetic mechanisms [ 67 ], being a significant contributor to the circadian effects of CAR, as shown in spinal astrocytes [ 68 ].…”

Section: Aging Cancer Susceptibility Pineal Melatonin and Cortisolmentioning

confidence: 99%

“…However, would this also be relevant in tumor pathogenesis? For example, GR driven SGK1, seems to induce a cancer stem-like phenotype [ 66 ], suggesting a possible impact on tumor pathogenesis, in association with heightened TDO/kynurenine/AhR mediated rise in the NAS/melatonin ratio in microenvironment cells. How relevant is the potentiation of GR nuclear translocation by Rb and the nuclear Rb/BAG-1 complex in cancer pathogenesis?…”

Section: Future Research Implicationsmentioning

confidence: 99%

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Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Anderson

2023

Exploration of Targeted Anti-Tumor Therapy

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A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications.

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Section: Aging Cancer Susceptibility Pineal Melatonin and Cortisolmentioning

confidence: 99%

Section: Future Research Implicationsmentioning

confidence: 99%

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Anderson

2023

Exploration of Targeted Anti-Tumor Therapy

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“…For ORAI1/STIM1 this is partly achieved by NFκΒ, which is also upregulated by SGK1 ( Lang et al, 2018a ). SGK1 is expressed in many tumors like colorectal ( Liang et al, 2017 , Chen et al, 2020 ), non-small cell lung cancer (NSCLC) ( Guerriero et al, 2020 , Kale et al, 2023 ), breast ( Godbole et al, 2018 , Al-Alem et al, 2023 , Zhang et al, 2023 ) and prostate ( Liu et al, 2017 , Liu et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells

Pantazaka,

Alkahtani,

Alarifi

et al. 2024

Saudi Pharmaceutical Journal

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SGK1 is involved in doxorubicin-induced chronic cardiotoxicity and dysfunction through activation of the NFκB pathway

Zhang,

Meng

et al. 2023

International Immunopharmacology

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Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients

Cited by 3 publications

References 37 publications

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells

SGK1 is involved in doxorubicin-induced chronic cardiotoxicity and dysfunction through activation of the NFκB pathway

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