Sphingosine-1-phosphate inhibits human keratinocyte proliferation via Akt/protein kinase B inactivation

Kim, Dong-Seok; Kim, Sook-Young; Kleuser, Burkhard; Schäfer‐Korting, Monika; Kim, Kyu Han; Park, Kyoung-Chan

doi:10.1016/s0898-6568(03)00114-1

Cited by 62 publications

(58 citation statements)

References 45 publications

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“…Current experimental therapies used to treat breast cancer (tamoxifen, retinoic acid, and GH-releasing hormone analogues) have led to a decrease of circulating IGF-I levels, suggesting that the antitumor effect of these agents, at least in part, is due to reduced circulating IGF-I (35,37,38). It is shown that the activation of IGF-I/IGF-IR/ IRS-1 leads to activation of two main proliferative pathways, the Ras-MAPK-extracellular signal-regulated kinase pathway and the phosphatidylinositol 3-kinase-AKT pathway, which stimulate cell cycle progression through cyclin D accumulation in the nucleus and inhibition of p27kip1 expression (39,40). Stimulation of IGF-IR/IRS-1 can also destabilize adhesion and stimulate cytoskeleton reorganization through modulation of the phosphorylation signals from adhesion molecules (integrins, RACK1, focal adhesion kinase, Cas, paxillin, E-cadherin; refs.…”

Section: Discussionmentioning

confidence: 99%

Absence of the Full-Length Breast Cancer–Associated Gene-1 Leads to Increased Expression of Insulin-Like Growth Factor Signaling Axis Members

Shukla¹,

Coumoul²,

Cao³

et al. 2006

Cancer Research

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The breast cancer-associated gene-1 (BRCA1) plays many important functions in multiple biological processes/pathways. Mice homozygous for a targeted deletion of full-length BRCA1 (Brca1 D11/D11 ) display both increased tumorigenesis and premature aging, yet molecular mechanisms underlying these defects remain elusive. Here, we show that Brca1 deficiency leads to increased expression of several insulin-like growth factor (IGF) signaling axis members in multiple experimental systems, including BRCA1-deficient mice, primary mammary tumors, and cultured human cells. Furthermore, we provide evidence that activation of IGF signaling by BRCA1 deficiency can also occur in a p53-independent fashion. Our data indicate that BRCA1 interacts with the IRS-1 promoter and inhibits its activity that is associated with epigenetic modification of histone H3 and histone H4 to a transcriptional repression chromatin configuration. We further show that BRCA1-deficient mammary tumor cells exhibit high levels of IRS-1, and acute suppression of Irs-1 using RNA interference significantly inhibits growth of these cells. Those observations provide a molecular insight in understanding both fundamental and therapeutic BRCA1-associated tumorigenesis and aging.

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Section: Discussionmentioning

confidence: 99%

Absence of the Full-Length Breast Cancer–Associated Gene-1 Leads to Increased Expression of Insulin-Like Growth Factor Signaling Axis Members

Shukla¹,

Coumoul²,

Cao³

et al. 2006

Cancer Research

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“…Recently, S1P has been shown to have signaling properties that regulate keratinocyte cell function (31)(32)(33)(34)(35)(36). Here, we report that the deletion of Sgpp1, the gene encoding SPP1, greatly disturbs epidermal homeostasis in mice.…”

Section: Sphingosine 1-phosphate (S1p)mentioning

confidence: 74%

Sphingosine-1-phosphate Phosphatase 1 Regulates Keratinocyte Differentiation and Epidermal Homeostasis

Allende

Sipe

Tuymetova

et al. 2013

Journal of Biological Chemistry

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Background: Sphingosine-1-phosphate phosphatase 1, encoded by Sgpp1, dephosphorylates the signaling lysophospholipid, S1P; however, its in vivo functions are not well understood. Results: Deletion of Sgpp1 causes epidermal defects with intrinsic keratinocyte abnormalities. Conclusion: Sgpp1 deficiency in keratinocytes causes S1P elevation and accelerates their differentiation. Significance: Intracellular S1P metabolism regulates keratinocyte differentiation and epidermal homeostasis.

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“…Since we discovered the S1P cancer growth inhibition effect, we excluded the growth promoting mechanisms as the signaling route. According to the literatures, Insulin‐like growth factors (IGFs) stimulated cell proliferation by activated MAPK, Akt 31 and S1P have been found to inhibit keratinocyte proliferation through inhibit Akt/PKB pathway induced by Insulin‐like growth factor I (IGF‐I) 32. In the cancer condition, triple negative breast cancer was reported to express high level of IGF‐I 31, 33.…”

Section: Discussionmentioning

confidence: 99%

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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Sphingosine-1-phosphate inhibits human keratinocyte proliferation via Akt/protein kinase B inactivation

Cited by 62 publications

References 45 publications

Absence of the Full-Length Breast Cancer–Associated Gene-1 Leads to Increased Expression of Insulin-Like Growth Factor Signaling Axis Members

Absence of the Full-Length Breast Cancer–Associated Gene-1 Leads to Increased Expression of Insulin-Like Growth Factor Signaling Axis Members

Sphingosine-1-phosphate Phosphatase 1 Regulates Keratinocyte Differentiation and Epidermal Homeostasis

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

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