Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival

Junttila, Melissa R.; Li, Song-Ping; Westermarck, Jukka

doi:10.1096/fj.06-7859rev

Cited by 704 publications

(657 citation statements)

References 132 publications

(178 reference statements)

Supporting

Mentioning

626

Contrasting

Unclassified

Order By: Relevance

“…53,54 Our findings suggest that MAPK signaling is involved in the local regulation of FGF23 in osteocytes, further highlighting the significance of this pathway in bone metabolism.…”

Section: Direct Regulation Of Fgf23 By Dmp1 J-w Lee Et Almentioning

confidence: 62%

Functional heterogeneity of osteocytes in FGF23 production: the possible involvement of DMP1 as a direct negative regulator

2014

View full text Add to dashboard Cite

Fibroblast growth factor 23 (FGF23) and dentin matrix protein (DMP1) are hallmarks of osteocytes in bone. However, the mechanisms underlying the actions of DMP1 as a local factor regulating FGF23 and bone mineralization are not well understood. We first observed spatially distinct distributions of FGF23-and DMP1-positive osteocytic lacunae in rat femurs using immunohistochemistry. Three-dimensional immunofluorescence morphometry further demonstrated that the distribution and relative expression levels of these two proteins exhibited reciprocally reversed patterns especially in midshaft cortical bone. These in vivo findings suggest a direct role of DMP1 in FGF23 expression in osteocytes. We next observed that the inoculation of recombinant DMP1 in UMR-106 osteoblast/osteocyte-like cells and long-cultured MC3T3-E1 osteoblastic cells showed significant downregulation of FGF23 production. This effect was rescued by incubation with an focal adhesion kinase (FAK) inhibitor or MEK (mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK)) inhibitor but not inhibitors of phosphoinositide 3-kinase or Rho kinase. Consistently, the levels of phosphorylated FAK, ERK and p38 were significantly elevated, indicating that exogenous DMP1 is capable of activating FAK-mediated MAPK signaling. These findings suggest that DMP1 is a local, direct and negative regulator of FGF23 production in osteocytes involved in the FAK-mediated MAPK pathway, proposing a relevant pathway that coordinates the extracellular environment of osteocytic lacunae and bone metabolism.

show abstract

“…53,54 Our findings suggest that MAPK signaling is involved in the local regulation of FGF23 in osteocytes, further highlighting the significance of this pathway in bone metabolism.…”

Section: Direct Regulation Of Fgf23 By Dmp1 J-w Lee Et Almentioning

confidence: 62%

Functional heterogeneity of osteocytes in FGF23 production: the possible involvement of DMP1 as a direct negative regulator

2014

View full text Add to dashboard Cite

show abstract

“…The mechanism of interaction between D scandens extract and radiation remains to be elucidated. Activation of ERK cascade has been reported to promote cell survival by regulating the expression or activity of pro-apoptotic proteins and anti-apoptotic members (Ewings et al, 2007;Junttila et al, 2008;Kohno et al, 2011). The evidence that D scandens extract decreases Erk1/2 activation in HT-29 cells suggests an inhibitory activity of the extract on this pro-survival pathway.…”

Section: Discussionmentioning

confidence: 99%

Ethanolic Extract from Derris scandens Benth Mediates Radiosensitzation via Two Distinct Modes of Cell Death in Human Colon Cancer HT-29 Cells

Hematulin

Ingkaninan²,

Limpeanchob³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells.

show abstract

“…Other AT extracts had small to moderate effects for decreasing the level of phosphoErk1/2 with the exception of WE, which had no effect relative to controls. Erk 1/2 activity is generally associated with mitogenesis and suppression of apoptosis (McCubrey et al, 2007;Junttila et al, 2008), and constitutive activation of Erk has been observed in prostate cancer (Gioeli et al, 1999;Uzgare and Isaacs, 2005). Erk 1/2 can activate a number of transcription factors, including NF-kB, to regulate gene expression (Raman et al, 2007;Kook et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

Wang

Li²,

Lu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-kB, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.

show abstract

Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival

Cited by 704 publications

References 132 publications

Functional heterogeneity of osteocytes in FGF23 production: the possible involvement of DMP1 as a direct negative regulator

Functional heterogeneity of osteocytes in FGF23 production: the possible involvement of DMP1 as a direct negative regulator

Ethanolic Extract from Derris scandens Benth Mediates Radiosensitzation via Two Distinct Modes of Cell Death in Human Colon Cancer HT-29 Cells

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

Contact Info

Product

Resources

About