PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma

Yan, Yonghong; Jin, Lei; Wilmott, James S.; Wang, Hu; Yosufi, Benafsha; Thorne, Rick F.; Liu, Tao; Rizos, Helen; Yan, Xu Guang; Dong, Lei; Tay, Kwang Hong; Tseng, Hsin‐Yi; Guo, Su; Bock, Charles E. de; Jiang, Chen Chen; Wang, Chun Yan; Wu, Mian; Zhang, Lin Jie; Hersey, Peter; Scolyer, Richard A.; Zhang, Xu Dong

doi:10.1038/ncomms2489

Cited by 67 publications

(107 citation statements)

References 57 publications

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“…85 Briefly, cells were seeded at 1,000 cells/well onto 6-well culture plates and allowed to grow for 24 h followed by the desired treatment. Cells were then allowed to grow for a further 12 d before fixation with methanol and staining with 0.5% crystal violet.…”

Section: Clonogenic Assaysmentioning

confidence: 99%

RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy

et al. 2015

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(2015) RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy, Autophagy, 11:7, 975-994, DOI: 10.1080/15548627.2015 Keywords: autophagy, cell death, endoplasmic reticulum stress, melanoma, RIPK1Abbreviations: 3-MA, 3-methyladenine; AMPK, AMP-activated protein kinase; ATF6, activating transcription factor 6; Baf A1, bafilomycin A 1 ; CAMKK2, calcium/calmodulin-dependent protein kinase kinase 2: b; EIF2AK3/PERK, eukaryotic translation initiation factor 2-a kinase 3; ER, endoplasmic reticulum; ERN1/IRE1, endoplasmic reticulum to nucleus signaling 1; HSF1, heat shock transcription factor 1; HSPA5, heat shock 70kDa protein 5 (glucose-regulated protein: 78kDa); MAP2K1/MEK1, mitogenactivated protein kinase kinase 1; MAPK, mitogen-activated protein kinase; MAPK1/ERK2, mitogen-activated protein kinase 1; MAPK3/ERK1, mitogen-activated protein kinase 3; MAPK8/JNK1, mitogen-activated protein kinase 8; MAPK9/JNK2, mitogenactivated protein kinase 9; MAPK11/p38b, mitogen-activated protein kinase 11; MAPK12/p38g, mitogen-activated protein kinase 12; MAPK13/p38d, mitogen-activated protein kinase 13; MAPK14/p38a, mitogen-activated protein kinase 14; NFKB1, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; PRKAA1, protein kinase AMP-activated: a 1 catalytic subunit; RIPK1, receptor (TNFRSF)-interacting protein kinase 1; SQSTM1/p62, sequestosome 1; TG, thapsigargin; TM, tunicamycin; TNFRSF1A/ TNFR1, tumor necrosis factor receptor superfamily: member 1A; UPR, unfolded protein response; XBP1, x-box binding protein 1.Although RIPK1 (receptor [TNFRSF]-interacting protein kinase 1) is emerging as a critical determinant of cell fate in response to cellular stress resulting from activation of death receptors and DNA damage, its potential role in cell response to endoplasmic reticulum (ER) stress remains undefined. Here we report that RIPK1 functions as an important prosurvival mechanism in melanoma cells undergoing pharmacological ER stress induced by tunicamycin (TM) or thapsigargin (TG) through activation of autophagy. While treatment with TM or TG upregulated RIPK1 and triggered autophagy in melanoma cells, knockdown of RIPK1 inhibited autophagy and rendered the cells sensitive to killing by TM or TG, recapitulating the effect of inhibition of autophagy. Consistently, overexpression of RIPK1 enhanced induction of autophagy and conferred resistance of melanoma cells to TM-or TG-induced cell death. Activation of MAPK8/JNK1 or MAPK9/JNK2, which phosphorylated BCL2L11/BIM leading to its dissociation from BECN1/Beclin 1, was involved in TM-or TG-induced, RIPK1-mediated activation of autophagy; whereas, activation of the transcription factor HSF1 (heat shock factor protein 1) downstream of the ERN1/IRE1-XBP1 axis of the unfolded protein response was responsible for the increase in RIPK1 in melanoma cells undergoing pharmacological ER stress. Collectively, these results identify upregulation of RIPK1 as an important resistance mechanism of melanoma cells to TM-or TG-induced ...

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Section: Clonogenic Assaysmentioning

confidence: 99%

RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy

et al. 2015

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“…Downregulation of PIB5PA, found in a proportion of melanomas, was due to histone hypoacetylation mediated by histone deacetylases through binding to the transcription factor Sp1 at the PIB5PA gene promoter. 42 HDAC inhibitors are being considered for the therapy of melanoma despite limited data available on posttranslational modifications of histones. 43 The histone methyltransferase SET Domain, Bifurcated 1 (SETDB1) is upregulated in melanoma and accelerates tumor development in zebrafish melanoma models harboring the BRAF V600E mutation.…”

Section: Histone Modificationmentioning

confidence: 99%

Epigenetic regulation in human melanoma: past and future

Sarkar

Leung

Baguley³

et al. 2015

Epigenetics

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“…PTEN is found to be commonly mutated or lost in numerous types of human cancers 30,31 , and monoallelic loss of PTEN is functionally haploinsufficient to facilitate tumour growth in the context of other somatic mutations 32 . INPP5J, an inositol 5-phosphatase recently identified, suppresses PI3K/Akt signalling by reducing the phosphorylation level of p-Akt (Ser 473) and was recently found to be downregulated in human melanoma, leading to promotion of cell proliferation and tumorigenicity in vivo 12,33 . Knockout of INPP4A was shown to sustain Akt activation and thereby promote cell proliferation, survival and tumorigenesis of mouse embryonic fibroblasts 13,34 .…”

Section: Discussionmentioning

confidence: 99%

miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma

et al. 2014

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The strength and duration of phosphoinositide signalling from phosphatidylinositol-3-kinase (PI3K) activation to Akt is tightly balanced by phosphoinositide kinases and phosphatases. However, how phosphatase-mediated negative regulatory effects are concomitantly disrupted in cancers, which commonly exhibit constitutively activated PI3K/Akt signalling, remains undefined. Here we report that miR-508 directly suppresses multiple phosphatases, including inositol polyphosphate-5-phosphatase J (INPP5J), phosphatase and tensin homologue (PTEN) and inositol polyphosphate 4-phosphatase type I (INPP4A), resulting in constitutive activation of PI3K/Akt signalling. Furthermore, we find that overexpressing miR-508 promotes, while silencing miR-508 impairs, the aggressive phenotype of oesophageal squamous cell carcinoma (ESCC) both in vitro and in vivo. Importantly, the level of miR-508 correlates with poor survival and activated PI3K/Akt signalling in a large cohort of ESCC specimens. These findings uncover a mechanism for constitutive PI3K/Akt activation in ESCC, and support a functionally and clinically relevant epigenetic mechanism in cancer progression.

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PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma

Cited by 67 publications

References 57 publications

RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy

RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy

Epigenetic regulation in human melanoma: past and future

miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma

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