Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling

Lamkin, Donald M.; Sloan, Erica K.; Patel, Ami J; Chiang, Beverley S; Pimentel, Matthew A.; Jeffrey, C Y; Arevalo, Jesusa M.G.; Morizono, Kouki; Cole, Steven W.

doi:10.1016/j.bbi.2012.01.013

Cited by 113 publications

(109 citation statements)

References 38 publications

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“…However, we determine that the rate of cell proliferation is not altered with isoproterenol or propranolol treatments (Fig. S1G), consistent with our findings for other cancer cell lines (Chang et al, 2016;Kim-Fuchs et al, 2014;Lamkin et al, 2012). Taken together, these findings suggest that the decreased cell deformability induced by isoproterenol treatment is associated with enhanced invasion and migration of cancer cells.…”

Section: Results βAr Signaling Reduces the Deformability Of Cancer Cellssupporting

confidence: 81%

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Kim

Gill

Nyberg

et al. 2016

Journal of Cell Science

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Invasion by cancer cells is a crucial step in metastasis. An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. β-adrenergic receptor (βAR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of β-adrenergic signaling by βAR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro. We find that βAR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that βAR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological β-blockade or genetic knockout of the β 2 -adrenergic receptor. Our results identify a β 2 -adrenergicCa 2+ -actin axis as a new regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion might be dependent on context.

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Section: Results βAr Signaling Reduces the Deformability Of Cancer Cellssupporting

confidence: 81%

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Kim

Gill

Nyberg

et al. 2016

Journal of Cell Science

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“…Lamkin et al [12] found that 2 weeks of daily restraint stress significantly enhanced the tumor burden and dissemination in a mouse model of acute lymphocyte leukemia. Breast cancer mice were prone to relapse during long-term injury impairment.…”

Section: Discussionmentioning

confidence: 99%

Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

Yu¹,

Zhuang²

2017

Acta Haematol

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Objectives: To explore the effect of the β-adrenoreceptor signaling pathway on myeloma cells. Methods: The myeloma U266 cell line was treated with epinephrine and propranolol. Cell proliferation was analyzed by MTS assay. Apoptosis was detected by flow cytometry. The β-receptor subtype and the key enzyme of epinephrine were identified by reverse transcription polymerase chain reaction (RT-PCR). Results: Epinephrine (5-50 μM) promoted U266 cell growth in a dose-dependent manner and neutralized the inhibition effect of bortezomib (25 and 50 ng/mL) in vitro. Cell proliferation was inhibited by a β-receptor antagonist, propranolol, at a concentration of 50-200 μM. The proportions of early and late apoptotic cells were enhanced after treatment with propranolol. The expression of caspase 3/7, 8, and 9 was elevated in propranolol-treated myeloma cells. Both β₁- and β₂-adrenoceptor mRNAs were expressed in the U266 cell line. Key enzymes dopamine hydroxylase and tyrosinehydroxylase were identified in myeloma cells. Conclusions: Our results reveal that epinephrine stimulates myeloma cell growth in vitro while the β-blocker propranolol has an antiproliferative effect, indicating that stress hormones may trigger the progression of myeloma.

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“…15,20,21,[23][24][25][26][27]29 Lastly, the bAR has been found to be important in regulating metastasis and/or migration in many other cancers, including pancreatic, [36][37][38] ovarian, 35 colorectal, 39 lung, 40 prostate, 18,36 and leukemia. 41,42 It will be interesting to investigate whether additional receptors are also promising targets to reduce breast cancer metastasis, and possibly metastasis of other solid cancers.…”

Section: Discussionmentioning

confidence: 99%

β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells

Wilson

Lorimer

Tyburski

et al. 2015

Cancer Biology & Therapy

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Keywords: adenosine receptor, breast cancer, cholera toxin, G protein-coupled receptor, protein isoprenylation, protein kinase A (PKA), Ras-related protein 1 (Rap1), b-adrenergic receptor Abbreviations: Adenosine 2B Receptor (A 2 BR), b-adrenergic receptor (bAR), Bay 60-6583 (Bay), Cholera toxin (Ctx), half time (T 1/2 ), Isoproterenol (Iso), G protein-coupled receptors (GPCR), Phosphate buffered saline (PBS), Protein kinase A (PKA), Propranolol (Prop).A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation and subsequent loss of Rap1B at the plasma membrane decreases cell-cell adhesion and increases cell scattering, which promotes the metastatic phenotype. Protein kinase A (PKA) was recently found to phosphorylate Rap1B and inhibit its prenylation. PKA is activated by G protein-coupled receptors (GPCR) that stimulate Ga s . In this study, we investigated whether the general Ga s activator, cholera toxin, and agonists of the b-adrenergic receptor (bAR), which is a Ga s -coupled GPCR, promote Rap1B phosphorylation and inhibit its prenylation. We show here that cholera toxin and bAR activation phosphorylate Rap1B and inhibit its prenylation and membrane localization, reducing cell-cell adhesion and promoting cell scattering. Furthermore, we report that breast cancer cell migration is decreased by the FDA-approved b-blocker, propranolol. Pharmacological targeting of GPCRs, especially those such as the bAR that are regulated by FDA-approved drugs, to increase cell adhesion and decrease cell scattering could provide a promising therapeutic approach to reduce breast cancer metastasis.

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Chronic stress enhances progression of acute lymphoblastic leukemia via β-adrenergic signaling

Cited by 113 publications

References 38 publications

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells

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