Paclitaxel induces Stathmin 1 phosphorylation, microtubule stability and apoptosis in acute lymphoblastic leukemia cells

Machado-Neto, João Agostinho; Alves, Ana Paula Nunes Rodrigues; Fernandes, Janainny Magalhães; Coelho-Silva, Juan Luiz; Scopim-Ribeiro, Renata; Fenerich, Bruna Alves; Silva, Fernanda Borges da; Scheucher, Priscila Santos; Simões, Belinda Pinto; Rego, Eduardo Magalhães; Traina, Fabı́ola

doi:10.1016/j.heliyon.2017.e00405

Cited by 10 publications

(5 citation statements)

References 21 publications

(29 reference statements)

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“…In addition, paclitaxel enhances stathmin phosphorylation in acute lymphoblastic leukemia cells and increases PP2A expression in non-small cell lung cancer (NSCLC) cells. 33,34) However, paclitaxel had no effect on stathmin phosphorylation and PP2A expression in ovarian cancer cells in this study. These results suggest that phosphorylation of stathmin induced by microtubuleassociated drugs, including eribulin and paclitaxel, might be differently regulated in different types of cancer cells.…”

Section: Discussioncontrasting

confidence: 61%

The Impact of Eribulin on Stathmin Dynamics and Paclitaxel Sensitivity in Ovarian Cancer Cells

Azumi

Yoshie

Takano

et al. 2022

Biological & Pharmaceutical Bulletin

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Eribulin, an inhibitor of microtubule dynamics, is used for treating breast cancers and sarcomas. The microtubule-destabilizing protein stathmin may modulate the antiproliferative activity of eribulin on breast cancer cells and leiomyosarcoma cells. The antitumor activity of eribulin in ovarian cancers has not been fully explored, so the present study aimed to determine the antitumor efficacy of eribulin and the involvement of stathmin in ovarian cancers. In a xenograft model of ovarian cancer, eribulin treatment reduced the tumor weight, which was accompanied by an increased level of phosphorylated stathmin. Eribulin stimulated the phosphorylation of stathmin in cultured cancer cell lines. The eribulin-induced phosphorylation of stathmin was inhibited by treatment with FTY720, an activator of protein phosphatase 2A (PP2A), and eribulin downregulated the expression of PP2A subunits. Furthermore, stathmin knockdown abrogated the inhibitory effects of eribulin on cell viability. Eribulin enhanced the antiproliferative effects of paclitaxel and concomitantly decreased stathmin expression. These results suggest that eribulin-induced phosphorylation of stathmin, mediated in part by PP2A downregulation, reduces stathmin activity and enhances the antiproliferative effects of paclitaxel in ovarian cancer. Collectively, the results of this study indicate that eribulin may suppress the proliferation of ovarian cancer cells partly by regulating the activity of stathmin.

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Section: Discussioncontrasting

confidence: 61%

The Impact of Eribulin on Stathmin Dynamics and Paclitaxel Sensitivity in Ovarian Cancer Cells

Azumi

Yoshie

Takano

et al. 2022

Biological & Pharmaceutical Bulletin

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“…Some studies show that chemotherapeutic agents that target microtubules affect the phosphorylation status of stathmin. Vinblastine, a microtubule destabilizer, increases stathmin phosphorylation in a non‐small cell lung cancer (NSCLC) cell line, 27 and Machado‐Neto et al 28 showed that PTX, a microtubule stabilizer, induces stathmin phosphorylation in acute lymphoblastic leukemia cells. Vinblastine reduces PP2A expression, whereas PTX increases it markedly, in NSCLC cells 27 .…”

Section: Discussionmentioning

confidence: 99%

Stathmin dynamics modulate the activity of eribulin in breast cancer cells

Yoshie

Ishida

Ohashi

et al. 2021

Pharmacology Res & Perspec

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Stathmin, a phosphoprotein that modulates microtubule dynamics, is highly expressed in breast cancer cells. Eribulin, a microtubule‐depolymerizing agent, is used to treat patients with advanced breast cancer. However, the detailed mechanisms underlying the action of eribulin during microtubule catastrophe, and the interaction between eribulin and stathmin dynamics, remain unclear. Here, we investigated the role of stathmin in the antiproliferative activity of eribulin in breast cancer cells. Eribulin induced phosphorylation of stathmin in MCF7 and MDA‐MB‐231 cells; this was attenuated by an inhibitor of protein kinase A (H89) and an inhibitor of Ca 2+ /calmodulin‐dependent kinase II (KN62). In addition, expression of phosphorylated stathmin was reduced by the protein phosphatase PP2A activator FTY720 but increased by the PP2A inhibitor okadaic acid. Of note, expression of PP2A subunits in eribulin‐treated cells decreased, although eribulin did not affect the phosphatase activity of recombinant PP2A directly. Furthermore, the antiproliferative effect of eribulin was stronger in stathmin‐overexpressing cells. These results suggest that stathmin dynamics are closely associated with the antiproliferative effects of eribulin and stathmin is a possible biomarker for predicting the therapeutic effects of eribulin in breast cancer patients.

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“…Stathmin (also known as stathmin 1, Op18, p18, p19, and metablastin) is a highly-conserved protein in various species and is essential for regulating the cell cycle [ 12 , 13 ], microtubules [ 14 , 15 ] and apoptosis [ 16 , 17 ]. Stathmin is reported to be involved in arsenic trioxide-induced apoptosis in human cervical cancer cell lines [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation

Lin

Chou

et al. 2021

Biomolecules

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Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV’s stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.

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Paclitaxel induces Stathmin 1 phosphorylation, microtubule stability and apoptosis in acute lymphoblastic leukemia cells

Cited by 10 publications

References 21 publications

The Impact of Eribulin on Stathmin Dynamics and Paclitaxel Sensitivity in Ovarian Cancer Cells

The Impact of Eribulin on Stathmin Dynamics and Paclitaxel Sensitivity in Ovarian Cancer Cells

Stathmin dynamics modulate the activity of eribulin in breast cancer cells

The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation

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