Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53

Carney, Bruce K.; Cassimeris, Lynne

doi:10.4161/cbt.9.9.11430

Cited by 24 publications

(85 citation statements)

References 43 publications

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Section: Introductionmentioning

confidence: 99%

“…We and others have shown that depleting stathmin in many cancer cell lines slows cell proliferation and ultimately leads to apoptosis (Alli et al 2007; Carney and Cassimeris 2010; Mistry et al 2005; Wang et al 2009; Zhang et al 2006). The slower proliferation observed in stathmin depleted cancer cells is likely a result not only of apoptosis, but also of a delay during G2 of the cell cycle (Carney and Cassimeris 2010). In contrast to cancer-derived cell lines, stathmin depletion is not deleterious to non-transformed cells (Carney and Cassimeris 2010; Zhang et al 2006) and stathmin knockout mice are viable (Schubart et al 1996).…”

Section: Introductionmentioning

confidence: 99%

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The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53

2012

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In several cancer cell lines, depleting the microtubule-destabilizing protein stathmin/oncoprotein18 leads to a G2 cell cycle delay and apoptosis. These phenotypes are observed only in synergy with low levels of p53, but the pathway(s) activated by stathmin depletion to delay the cell cycle are unknown. We found that stathmin depletion caused greater microtubule stability in synergy with loss of p53, measured by the levels of acetylated α-tubulin and the rate of centrosomal microtubule nucleation. Nocodazole or vinblastine-induced microtubule depolymerization abrogated the stathmin-depletion induced G2 delay, measured by the percentage of cells staining positive for several markers (TPX2, CDK1 with inhibitory phosphorylation), indicating that microtubules are required to lengthen G2. Live cell imaging showed that stathmin depletion increased time in G2 without an impact on the duration of mitosis, indicating that the longer interphase duration is not simply a consequence of a previous slowed mitosis. In contrast, stabilization of microtubules with paclitaxel (8 nM) slowed mitosis without lengthening the duration of interphase, demonstrating that increased microtubule stability alone is not sufficient to delay cells in G2.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53

2012

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“…[56] Furthermore, depletion of stathmin leads to cell cycle arrest in the G2 phase and apoptosis. [57] Due to the known correlation between stathmin expression level and other epithelial cancers, the differential expression of stathmin detected between the thymoma tumor types was further investigated using IHC. The IHC staining showed that the stathmin was localized to the T lymphocytes infiltrating the biopsy tissue, leading to the conclusion that stathmin is a lymphocyte associated protein.…”

Section: Discussionmentioning

confidence: 99%

“…The positive staining of stathmin in T lymphocytes is supported by previous studies, as stathmin plays a critical role in the activation of T lymphocytes as a regulator of cell polarization and T lymphocyte migration from the vascular compartment across tissue barriers. [57, 58] The use of stathmin to distinguish the different thymoma subtypes is limited due to its staining of lymphocytes as opposed to the tumorous epithelial cells themselves, as CD4 and CD8 are well-established IHC targets for T lymphocytes. [59]…”

Section: Discussionmentioning

confidence: 99%

Proteomic Signatures of Thymomas

et al. 2016

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Based on the histological features and outcome, the current WHO classification separates thymomas into A, AB, B1, B2 and B3 subtypes. It is hypothesized that the type A thymomas are derived from the thymic medulla while the type B thymomas are derived from the cortex. Due to occasional histological overlap between the tumor subtypes creating difficulties in their separation, the aim of this study was to provide their proteomic characterization and identify potential immunohistochemical markers aiding in tissue diagnosis. Pair-wise comparison of neoplastic and normal thymus by liquid chromatography tandem mass spectrometry (LC-MS/MS) of formalin fixed paraffin embedded tissue revealed 61 proteins differentially expressed in thymomas compared to normal tissue. Hierarchical clustering showed distinct segregation of subtypes AB, B1 and B2 from that of A and B3. Most notably, desmoyokin, a protein that is encoded by the AHNAK gene, was associated with type A thymomas and medulla of normal thymus, by LC-MS/MS and immunohistochemistry. In this global proteomic characterization of the thymoma, several proteins unique to different thymic compartments and thymoma subtypes were identified. Among differentially expressed proteins, desmoyokin is a marker specific for thymic medulla and is potentially promising immunohistochemical marker in separation of type A and B3 thymomas.

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“…As a more direct measure of cell death, trypan blue exclusion assays were performed as described previously (13).…”

Section: Cell Survival Assaysmentioning

confidence: 99%

Microtubule Control of Metabolism in Prostate Cancer

Cassimeris¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe current standard chemotherapy treatment for metastatic castrate-resistant prostate cancer is the microtubule-stabilizing drug, docetaxel, but the median increase in survival is limited to several months. One avenue for improved treatment outcome is to find agents that increase cell death when combined with docetaxel.Here we tested whether two metabolic inhibitors, metformin or 2-deoxy-glucose, function synergistically with docetaxel to block prostate cancer cell proliferation. LNCaP and PC-3 prostate cancer cell lines were incubated in drugs targeting the microtubule cytoskeleton (docetaxel, paclitaxel, or nocodazole) singly, or in combination with metabolic inhibitors (metformin or 2-deoxy-glucose). Microtubule-targeted drugs, which either stabilize or destabilize microtubules, acted synergistically with either metformin or 2-deoxy-glucose to block cell proliferation and cause cell death in both prostate cancer cell lines tested. Synergy was consistently calculated at the ED50 for each drug, but for many drug combinations, the combination index shifted toward antagonism at higher drug doses. Microtubule stabilizers (docetaxel, paclitaxel) showed greater synergy than did a microtubule destabilizer (nocodazole) when combined with either of the metabolic inhibitor tested. The more-thanadditive cell killing measured in two commonly used prostate cancer lines treated with a mixture of microtubule-targeted drugs and metabolic inhibitors indicates that these drug combinations could provide more effective tumor cell killing than either drug alone. SUBJECT TERMSNone provided. IntroductionProstate cancer is the second leading cause of cancer deaths for men in the United States (American Cancer Society, 2013 statistics). Although often cured by surgery or radiation treatment, for many patients the disease progresses from one responsive to androgen removal to one where cancer cells have become androgen insensitive, the latter termed metastatic castrate-resis...

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Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53

Cited by 24 publications

References 43 publications

The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53

The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53

Proteomic Signatures of Thymomas

Microtubule Control of Metabolism in Prostate Cancer

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