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<p>Glioblastoma (GBM) is the most common primary malignant brain tumor in the central nervous system, characterized by high invasiveness, incidence, and mortality. Tubulin folding cofactor B (TBCB) is a microtubule-associated regulator implicated in microtubule plus-end organization and related structural features; however, its role and underlying mechanisms in GBM remain unclear. This study aimed to elucidate the function and mechanisms of TBCB in GBM cell proliferation and migration. Analyses of public databases (GEO, TCGA, CGGA) and clinical GBM specimens revealed that TBCB was significantly upregulated in GBM compared with normal controls, with higher expression correlating with higher WHO grades and poor prognosis. Functionally, TBCB knockdown in U87 and U251 cells significantly inhibited proliferation and migration (assessed by EdU, cell counting, Transwell and wound-healing assays) and impaired cell process formation; consistently, in vivo experiments using orthotopic intracranial xenograft models confirmed that TBCB knockdown suppressed tumor growth and prolonged survival. Mechanistically, reciprocal Co-IP/IF supported association of TBCB with both EB1 and EB3, indicating that TBCB acts as a functional partner of the microtubule plus-end tracking proteins ( + TIPs) EB1 and EB3, co-localizing at cell process tips and being associated with microtubule plus-end organization/comet-like features. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified the MAPK pathway as a key signaling pathway associated with TBCB; Western blotting showed that TBCB knockdown reduced the p-ERK/ERK ratio, and pharmacological modulation with the ERK agonist TPA and the MEK inhibitor U0126 further indicated that ERK-pathway perturbation regulates TBCB in a time-dependent and nonlinear manner in GBM cells. Collectively, these findings indicate that TBCB promotes GBM cell proliferation and migration through EB1/EB3-associated microtubule plus-end organization and is functionally coupled to the ERK–MAPK pathway in a time-dependent and nonlinear manner, suggesting that TBCB is a candidate regulator of GBM progression that warrants further translational validation.</p>

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The role and mechanism of tubulin folding cofactor B in glioblastoma migration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Bingqiu Zhang,
  • Qiang Wang,
  • Chenglong Ouyang,
  • Mei Yang,
  • Qiuxi Chen,
  • Xiaoqiao Chen,
  • Fei Gao,
  • Hui Liu

摘要

Glioblastoma (GBM) is the most common primary malignant brain tumor in the central nervous system, characterized by high invasiveness, incidence, and mortality. Tubulin folding cofactor B (TBCB) is a microtubule-associated regulator implicated in microtubule plus-end organization and related structural features; however, its role and underlying mechanisms in GBM remain unclear. This study aimed to elucidate the function and mechanisms of TBCB in GBM cell proliferation and migration. Analyses of public databases (GEO, TCGA, CGGA) and clinical GBM specimens revealed that TBCB was significantly upregulated in GBM compared with normal controls, with higher expression correlating with higher WHO grades and poor prognosis. Functionally, TBCB knockdown in U87 and U251 cells significantly inhibited proliferation and migration (assessed by EdU, cell counting, Transwell and wound-healing assays) and impaired cell process formation; consistently, in vivo experiments using orthotopic intracranial xenograft models confirmed that TBCB knockdown suppressed tumor growth and prolonged survival. Mechanistically, reciprocal Co-IP/IF supported association of TBCB with both EB1 and EB3, indicating that TBCB acts as a functional partner of the microtubule plus-end tracking proteins ( + TIPs) EB1 and EB3, co-localizing at cell process tips and being associated with microtubule plus-end organization/comet-like features. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified the MAPK pathway as a key signaling pathway associated with TBCB; Western blotting showed that TBCB knockdown reduced the p-ERK/ERK ratio, and pharmacological modulation with the ERK agonist TPA and the MEK inhibitor U0126 further indicated that ERK-pathway perturbation regulates TBCB in a time-dependent and nonlinear manner in GBM cells. Collectively, these findings indicate that TBCB promotes GBM cell proliferation and migration through EB1/EB3-associated microtubule plus-end organization and is functionally coupled to the ERK–MAPK pathway in a time-dependent and nonlinear manner, suggesting that TBCB is a candidate regulator of GBM progression that warrants further translational validation.