SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

Tanti, Goutam Kumar; Pandey, Shivendra Kumar; Goswami, Shyamal

doi:10.1016/j.bbrc.2015.05.069

Cited by 20 publications

(10 citation statements)

References 37 publications

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“…STRN3 interacts with AKT and PARK7 via the WD-40 domains and a region further upstream of the WD-40 repeats, respectively [116]. STRN3 also increases the expression of PARK7 by inhibiting the proteasome-mediated degradation of PARK7 and subsequently activates AKT by enhancing the stability of PARK7 and increasing the formation of protein-protein complexes for protecting cancer cells from oxidative stress [117]. Moreover, the stability of PARK7 is markedly increased by the loss of function of TP53, and PARK7 induces the activation of TP53 during oxidative stress.…”

Section: Positive Modulators Of Park7 Expressionmentioning

confidence: 99%

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

Jin

2020

JCM

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The expression of PARK7 is upregulated in various types of cancer, suggesting its potential role as a critical regulator of the pathogenesis of cancer and in the treatment of cancer and neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and Huntington disease. PARK7 activates various intracellular signaling pathways that have been implicated in the induction of tumor progression, which subsequently enhances tumor initiation, continued proliferation, metastasis, recurrence, and resistance to chemotherapy. Additionally, secreted PARK7 has been identified as a high-risk factor for the pathogenesis and survival of various cancers. This review summarizes the current understanding of the correlation between the expression of PARK7 and tumor progression.

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Section: Positive Modulators Of Park7 Expressionmentioning

confidence: 99%

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

Jin

2020

JCM

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“…The relationship between STRN and tumours has attracted researchers' attentions in recent years. For example, STRN3 was reported to activate the Akt signalling pathway to enhance the survival of cancer cells [21]. Silencing of the STRN4 protein in many tumour cells can inhibit their proliferation, invasion, and migration [14].…”

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confidence: 99%

High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition

Yao

Zhou

et al. 2020

BioMed Research International

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A STRN-ALK fusion protein has been recently identified as a potential therapeutic target in multiple cancers; however, the role of STRN alone in regulating the biological function of hepatocellular carcinoma (HCC) remains unclear. In this study, we firstly detected an overexpression of STRN in HCC tissues compared to that in adjacent nontumour (ANT) tissues through IHC analysis, and the expression level of this protein was positively correlated with lymph node metastasis and TNM stage. In vitro, high expression of STRN was also confirmed in different HCC cell lines, and regulation of STRN expression in Huh7 cells did not significantly affect tumour cell proliferation or apoptosis but was positively correlated with tumour cell invasion and migration capacities. Moreover, both the knockdown and overexpression of STRN in Huh7 cells can lead to cell morphological changes that are accompanied with an alteration of epithelial-mesenchymal transition (EMT) molecular markers E-cadherin and Vimentin. Finally, STRN was further proved to be negatively related to E-cadherin expression but positively related to Vimentin expression in human HCC tissue samples. Taken together, STRN is upregulated in HCC and acts as a tumour promoter regulating cell invasion and migration through facilitating the EMT process.

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“…Because of extensive conservation of various sequence motifs, variants of SG2NA are expected to have overlapping but distinct function. Down regulation of SG2NA by shRNA makes Neuro2A cells more susceptible to oxidative stress but specific contribution by each variant is yet to be determined 13 .…”

Section: Introductionmentioning

confidence: 99%

GSK3β and ERK regulate the expression of 78 kDa SG2NA and ectopic modulation of its level affects phases of cell cycle

Pandey

Talukdar

Jain

et al. 2017

Sci Rep

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Striatin and SG2NA are essential constituents of the multi-protein STRIPAK assembly harbouring protein phosphatase PP2A and several kinases. SG2NA has several isoforms generated by mRNA splicing and editing. While the expression of striatin is largely restricted to the striatum in brain, that of SG2NAs is ubiquitous. In NIH3T3 cells, only the 78 kDa isoform is expressed. When cells enter into the S phase, the level of SG2NA increases; reaches maximum at the G2/M phase and declines thereafter. Downregulation of SG2NA extends G1 phase and its overexpression extends G2. Ectopic expression of the 35 kDa has no effects on the cell cycle. Relative abundance of phospho-SG2NA is high in the microsome and cytosol and the nucleus but low in the mitochondria. Okadoic acid, an inhibitor of PP2A, increases the level of SG2NA which is further enhanced upon inhibition of proteasomal activity. Phospho-SG2NA is thus more stable than the dephosphorylated form. Inhibition of GSK3β by LiCl reduces its level, but the inhibition of ERK by PD98059 increases it. Thus, ERK decreases the level of phospho-SG2NA by inhibiting GSK3β. In cells depleted from SG2NA by shRNA, the levels of pGSK3β and pERK are reduced, suggesting that these kinases and SG2NA regulate each other’s expression.

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SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

Cited by 20 publications

References 37 publications

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition

GSK3β and ERK regulate the expression of 78 kDa SG2NA and ectopic modulation of its level affects phases of cell cycle

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