Class III β‐tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer

Donato, Marta De; Mariani, Marisa; Petrella, Lella; Martinelli, Elisa; Zannoni, Gian Franco; Vellone, Valerio Gaetano; Ferrandina, Gabriella; Shahabi, Shohreh; Ferlini, Cristiano

doi:10.1002/jcp.22813

Cited by 61 publications

(81 citation statements)

References 24 publications

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“…D, a graph showing that reexpression of bIII-tubulin (H460 pRS/bIII R17) abolished the increased sensitivity to anoikis in bIII-tubulin shRNA H460 NSCLC cells (H460 pRS/bIIISH4); n ¼ 3 independent experiments ( Ã , P < 0.05 H460 pRS/bIIISH4 vs. pRS/CtrlSH2; #P < 0.05 pRS/bIIISH4 vs. pRS/bIII R17). (36,37). Furthermore, binding to these proteins initiated signaling cascades, which promoted cellular survival under stress conditions.…”

Section: Discussionmentioning

confidence: 99%

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

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bIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence is not understood. Functional and differential proteomics revealed that bIII-tubulin regulates expression of proteins associated with malignant growth and metastases. In particular, the adhesionassociated tumor suppressor maspin was differentially regulated by bIII-tubulin. Functionally, bIII-tubulin suppression altered cell morphology, reduced tumor spheroid outgrowth, and increased sensitivity to anoikis. Mechanistically, the PTEN/AKT signaling axis was defined as a critical pathway regulated by bIII-tubulin in NSCLC cells. bIII-Tubulin blockage in vivo reduced tumor incidence and growth. Overall, our findings revealed how bIII-tubulin influences tumor growth in NSCLC, defining new biologic functions and mechanism of action of bIII-tubulin in tumorigenesis.Cancer Res; 75(2); 415-25. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

et al. 2015

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“…Currently, little is known about cellular partners of GBP-1. It is known that GBP-1 binds (besides homodimerization and heterodimerization with GBP family members) (41,42) to the cytoskeletal proteins b-IIITubulin and PIM1 (14). Five among the 10 potential GBP-1 binding partners identified by us by mass spectrometry (multisynthetase complex auxiliary component p43, plastin-2, STOML2, MRCL3, and bIIspectrin) are described to be involved in the remodeling of the (actin-) cytoskeleton (33,36,43,44) and 4 of these 5 (plastin-2, STOML2, MRCL3, and bII-spectrin) to influence T cell activation (30,(32)(33)(34)(35)(36)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, GBP-1 interferes with hepatitis C virus infection through interaction with the viral protein NS5B (13). The only cellular interaction partner of GBP-1 known so far is b-IIITubulin (14). This points to interaction of GBP-1 with structural proteins and suggests that overexpression of GBP-1 in paclitaxel-resistant cells is directly associated to the therapeutic failure of this antimitotic drug in certain tumors (15).…”

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confidence: 99%

Guanylate Binding Protein 1–Mediated Interaction of T Cell Antigen Receptor Signaling with the Cytoskeleton

Förster

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Supper

et al. 2014

The Journal of Immunology

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GTPases act as important switches in many signaling events in cells. Although small and heterotrimeric G proteins are subjects of intensive studies, little is known about the large IFN-inducible GTPases. In this article, we show that the IFN-γ–inducible guanylate binding protein 1 (GBP-1) is a regulator of T cell activation. Silencing of GBP-1 leads to enhanced activation of early T cell Ag receptor/CD3 signaling molecules, including Lck, that is translated to higher IL-2 production. Mass spectrometry analyses showed that regulatory cytoskeletal proteins, like plastin-2 that bundles actin fibers and spectrin β-chain, brain 1 that links the plasma membrane to the actin cytoskeleton, are binding partners of GBP-1. The spectrin cytoskeleton influences cell spreading and surface expression of TCR/CD3 and the leukocyte phosphatase CD45. We found higher cell spreading and enhanced surface expression of TCR/CD3 and CD45 in GBP-1 silenced T cells that explain their enhanced TCR/CD3 signaling. We conclude that GBP-1 is a downstream processor of IFN-γ via which T cells regulate cytoskeleton-dependent cell functions.

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“…and AR reverse 5 0 -TGGAATAATGCTGAAGAGT-3 0 . Other primers were previously reported (13). To normalize the possible variation in sample concentration, we used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as housekeeping control, as previously described (12).…”

Section: Translational Relevancementioning

confidence: 99%

“…Although in these cells we were unable to obtain the AR silencing, we did not observe any relevant change in terms of TUBB3/TUBB6 expression (data not shown). In parallel with the silencing of TUBB3/TUBB6, we also measured the expression of PIM1, a protein kinase that is intimately bound to the TUBB3 function (13). Also this gene exhibited the same trend of downregulation.…”

Section: Immunohistochemical Analysis Of Tubb3 and Tubb6 Expression Imentioning

confidence: 99%

Gender Influences the Class III and V β-Tubulin Ability to Predict Poor Outcome in Colorectal Cancer

Mariani

Zannoni

Sioletic

et al. 2012

Clinical Cancer Research

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Purpose: Colorectal cancer is one of the deadliest diseases in Western countries. To predict the outcome of therapy, we assessed the role of class III (TUBB3) and class V b-tubulin (TUBB6) as predictive biomarkers.Experimental Design: Using immunohistochemistry and nanofluidics, the expression of TUBB3 and TUBB6 was assessed in two cohorts of 180 and 134 patients, respectively. The CYP17A1 RS743572 was genotyped to identify GG carriers with enhanced androgen levels. TUBB3 and TUBB6 were investigated in 22 colorectal cancer cell lines in basal conditions and after serum starvation, the latter serving as activator of this prosurvival pathway. To ascertain the role of androgen receptor (AR) in such regulation, we silenced AR and checked TUBB3 and TUBB6 expression and sensitivity to chemotherapy.Results: There was a link between poor survival, the expression of TUBB3/TUBB6, and AR only in females. Conversely, only in males carriers of the GG phenotype exhibited the worst outcome. Importantly, male cell lines were resistant to serum starvation and exhibited higher levels of TUBB6, thereby suggesting that the pathway is activated by androgens. In female cells this phenomenon was absent. In both genders, AR was the main driver of TUBB3/TUBB6 expression, as constitutive silencing of AR was associated with downregulation of TUBB3/TUBB6 expression and increased sensitivity to oxaliplatin and SN-38.Conclusions: The involvement of androgens in the TUBB3 pathway opens the way for clinical trials to assess the efficacy of antiandrogens for increasing the efficacy of chemotherapy in male colorectal cancer patients.

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Class III β‐tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer

Cited by 61 publications

References 24 publications

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer

Guanylate Binding Protein 1–Mediated Interaction of T Cell Antigen Receptor Signaling with the Cytoskeleton

Gender Influences the Class III and V β-Tubulin Ability to Predict Poor Outcome in Colorectal Cancer

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