βIII-Tubulin Gene Regulation in Health and Disease

Duly, Alastair; Kao, Felicity C L; Teo, Wee Siang; Kavallaris, Maria

doi:10.3389/fcell.2022.851542

Cited by 35 publications

(21 citation statements)

References 159 publications

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“…4G). Another common marker for early immature neurons is TUBB3 , which encodes a microtubule element of the β-tubulin protein family that influences neurogenesis and axon guidance ( 60 ). The relative abundance of TUBB3 was significantly increased in cells within both DYN gels compared to the Static gels (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tunable hydrogel viscoelasticity modulates human neural maturation

Roth,

Huang,

Navarro

et al. 2023

Sci. Adv.

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Human-induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biomechanical signaling cues imparted by the extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in neural maturation gene expression. Together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.

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Section: Resultsmentioning

confidence: 99%

Tunable hydrogel viscoelasticity modulates human neural maturation

Roth,

Huang,

Navarro

et al. 2023

Sci. Adv.

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“…All three genes had been already identified in the limb both at the MuSC levels and in entire muscles in the adult (Evano et al, 2020b; Honda et al, 2017; Terry et al, 2018). Pcdh7, an integral membrane protein belonging to cadherin superfamily that regulates intercellular adhesion (Wang et al, 2020; Yoshida, 2003) is unique to TA quiescent state and the microtubule protein Tubb3 (Duly et al, 2022) is a marker marker of the TA activated state (Figure 3I).…”

Section: Resultsmentioning

confidence: 99%

Extraocular muscle stem cells exhibit distinct cellular properties associated with non-muscle molecular signatures

Girolamo

Benavente-Diaz

Grimaldi

et al. 2023

Preprint

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The muscle stem cell (MuSC) population is recognized as functionally heterogeneous. Cranial muscle stem cells, which originate from head mesoderm, can have greater proliferative capacity in culture and higher regenerative potential in transplantation assays when compared to those in the limb. The existence of such functional differences in phenotypic outputs remain unresolved as a comprehensive understanding of the underlying mechanisms is lacking. We addressed this issue using a combination of clonal analysis, live imaging, and scRNA-seq, identifying critical biological features that distinguish extraocular (EOM) and limb (Tibialis anterior, TA) MuSC populations. Time-lapse studies using a MyogenintdTomato reporter showed that the increased proliferation capacity of EOM MuSCs is accompanied by a differentiation delay in vitro. Unexpectedly, in vitro activated EOM MuSCs expressed a large array of distinct extracellular matrix (ECM) components, growth factors, and signaling molecules that are typically associated with mesenchymal non-muscle cells. These unique features are regulated by a specific set of transcription factors that constitute a coregulating module. This transcription factor network, which includes Foxc1 as one of the major players, appears to be hardwired to EOM identity as it is present in quiescent adult MuSCs, in the activated counterparts during growth and retained upon passages in vitro. These findings provide insights into how high-performing MuSCs regulate myogenic commitment by active remodeling of their local environment.

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“…The largest change in expression in the cytoplasmic fraction was observed for TUBB3 (tubulin beta III) - a microtubule protein with important roles in chromosome segregation during mitosis, which was shown to be overexpressed in some cancers in a cell-cycle dependent manner, its overexpression leading to resistance to taxane derivates [41], advanced tumor stage, and HER2 amplification in patient cohorts [42]. The mechanisms that lead to TUBB3 expression dysregulation in cancer cells have not been, however, clarified yet [43].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors

Karcini,

Mercier,

Lazar

2024

Preprint

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Modern cancer treatment approaches aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eliminate the cancer cells. To overcome a relatively short-lived response due to the development of resistance to the administered drugs, combination therapies have been pursued, as well. To expand the outlook of combination therapies, the objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the response of HER2+ breast cancer cells to a mixture of two kinase inhibitors that has not been adopted yet as a standard treatment regime. The broader landscape of biological processes that are affected by inhibiting two major pathways that sustain the growth and survival of cancer cells, i.e., EGFR and PI3K/AKT, was investigated by treating SKBR3/HER2+ breast cancer cells with Lapatinib or a mixture of Lapatinib/Ipatasertib small molecule drugs. Changes in protein expression and/or activity in response to the drug treatments were assessed by using two complementary quantitative proteomic approaches based on peak area and peptide spectrum match measurements. Over 900 proteins matched by three unique peptide sequences (FDR<0.05) were affected by the exposure of cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib, and, in addition to cell cycle and growth arrest processes enabled the identification of several multi-functional proteins with roles in cancer-supportive hallmark processes. Among these, immune response, adhesion and migration emerged as particularly relevant to the ability to effectively suppress the proliferation and dissemination of cancer cells. The supplementation of Lapatinib with Ipatasertib further affected the expression or activity of additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the affected proteins represented approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners. Altogether, our findings exposed a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways. The data are available via ProteomeXchange with identifier PXD051094.

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βIII-Tubulin Gene Regulation in Health and Disease

Cited by 35 publications

References 159 publications

Tunable hydrogel viscoelasticity modulates human neural maturation

Tunable hydrogel viscoelasticity modulates human neural maturation

Extraocular muscle stem cells exhibit distinct cellular properties associated with non-muscle molecular signatures

Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors

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