Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells

Godbole, Mukul; Togar, Trupti; Patel, Kuldeep; Dharavath, Bhasker; Yadav, Neelima; Janjuha, Sharan; Gardi, Nilesh; Tiwary, Kanishka; Terwadkar, Prachi; Desai, Sanket; Prasad, Ratnam; Dhamne, Hemant; Karve, Kunal; Salunkhe, Sameer; Kawle, Dhananjay; Chandrani, Pratik; Dutt, Shilpee; Gupta, Sudeep; Badwe, Rajendra; Dutt, Amit

doi:10.1074/jbc.ra118.002894

Cited by 29 publications

(40 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HIF-regulated N-myc downstream regulated gene (NDRG1) is predominantly overexpressed in perinecrotic areas and ER-negative breast cancer and is predictive for bevacizumab response and prognostic for survival (80,81). Homozygous loss-of-function NDRG1 in humans causes a neurological disorder with nerve demyelination and NDRG1 manipulation in breast cancer cell lines deregulated lipid droplet storage, although its exact metabolic function and discrepancies in its reported effects on migration and breast cancer progression require further clarification (81,82).…”

Section: Lipid Metabolismmentioning

confidence: 99%

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

238

146

View full text Add to dashboard Cite

Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in breast cancer patients. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

show abstract

Section: Lipid Metabolismmentioning

confidence: 99%

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

238

146

View full text Add to dashboard Cite

show abstract

“…Posttranscriptional regulation, including RNA processing, RNA degradation and translation is an essential aspect of the regulation of gene expression. Previous studies demonstrated that the disorder of posttranscriptional regulation is associated with the occurrence and development of various cancers [21][22][23]. Many RBPs bind to sequence-speci c motifs or RNA secondary structures through unique modular arrangements of individual RNA-binding domains to play the roles in the homeostatic regulation of gene expression [24,25], which in uence the progression of many diseases.…”

Section: Discussionmentioning

confidence: 99%

Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer

Zhang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Gastric cancer (GC) is one of the most common cancers with high incidence and mortality worldwide. Recently, RNA-binding proteins (RBPs) have drawn more and more attention for its role in cancer pathophysiology. In this study, we aim to explore the function and clinical implication of RBPs in GC. Methods: RNA sequencing data along with the corresponding clinical information of GC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA-binding proteins (DERBPs) between tumor and normal tissues were identified by ‘limma’ package. Functional enrichment analysis and the protein-protein interaction (PPI) network were harnessed to explore the function and interaction of DERBPs. Next, Univariate and multiple Cox regression were applied to screen prognosis-related hub RBPs and to construct a signature for BC. Meanwhile, a nomogram was built based on the same RBPs. Results: A total of 296 DERBPs were found, and most of them mainly related to post-transcriptional regulation of RNA and ribonucleoprotein. A PPI network of DERBPs was constructed, consisting of 262 nodes and 2567 edges. A prognostic signature was built depended on seven prognosis-related hub RBPs that could divide GC patients into high- and low-risk groups. Survival analysis showed that the high-risk group had a worse prognosis compared to the low-risk group and the time-dependent receiver operating characteristic (ROC) curves suggested that the signature existed moderate predictive capacities of survival for GC patients. Similar results were obtained from another independent set GSE84437, confirming the robustness of signature. Calibration plots reported good consistency between overall survival (OS) prediction by nomogram and actual observation. Conclusion: The findings of this study would provide evidence of the effect of RBPs on GC as well as offering novel potential biomarkers in prognosis prediction and clinical decision for GC patients.

show abstract

“…Increased NDRG1 expression reduced the activation of multiple cellular kinases and cell migration. 21 These inconsistent views may be due to the different models used, suggesting that SGK1 performs specific functions in different situations.…”

Section: Functions and Mechanisms Of Sgk1 In Oncologymentioning

confidence: 99%

“… 1 , 3 , 14 , 15 SGK1 has been previously reported in hypertension, diabetes, hypercoagulability, and autoimmune disease. 5 , 16 , 17 A growing number of recent studies reveal a role for SGK1 in human tumors such as glioblastoma, 18 – 20 breast, 21 – 25 colorectal, 26 – 28 prostate, 29 – 31 thyroid, 32 ovarian, 33 myeloma, 11 and non-small cell lung cancer 34 ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star

Zhu

Cao

et al. 2020

Ther Adv Med Oncol

View full text Add to dashboard Cite

Serum and glucocorticoid-inducible kinase 1 (SGK1) is an AGC kinase that has been reported to be involved in a variety of physiological and pathological processes. Recent evidence has accumulated that SGK1 acts as an essential Akt-independent mediator of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in cancer. SGK1 is overexpressed in several tumors, including prostate cancer, colorectal carcinoma, glioblastoma, breast cancer, and endometrial cancer. The functions of SGK1 include regulating tumor growth, survival, metastasis, autophagy, immunoregulation, calcium (Ca2+) signaling, cancer stem cells, cell cycle, and therapeutic resistance. In this review, we introduce the pleiotropic role of SGK1 in the development and progression of tumors, summarize its downstream targets, and integrate the knowledge provided by preclinical studies that the prospect of SGK1 inhibition as a potential therapeutic approach.

show abstract

Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells

Cited by 29 publications

References 45 publications

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer

The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star

Contact Info

Product

Resources

About