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Medical Molecular Morphology
Published in: Medical Molecular Morphology 1/2024

06-11-2023 | Pancreatic Cancer | Original Paper

Δ3-tubulin impairs mitotic spindle morphology and increases nuclear size in pancreatic cancer cells

Authors: Kenta Baba, Kenichiro Uemura, Ryota Nakazato, Faryal Ijaz, Shinya Takahashi, Koji Ikegami

Published in: Medical Molecular Morphology | Issue 1/2024

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Abstract

Cancer cell proliferation is affected by post-translational modifications of tubulin. Especially, overexpression or depletion of enzymes for modifications on the tubulin C-terminal region perturbs dynamic instability of the spindle body. Those modifications include processing of C-terminal amino acids of α-tubulin; detyrosination, and a removal of penultimate glutamic acid (Δ2). We previously found a further removal of the third last glutamic acid, which generates so-called Δ3-tubulin. The effects of Δ3-tubulin on spindle integrities and cell proliferation remain to be elucidated. In this study, we investigated the impacts of forced expression of Δ3-tubulin on the structure of spindle bodies and cell division in a pancreatic cancer cell line, PANC-1. Overexpression of HA-tagged Δ3-tubulin impaired the morphology and orientation of spindle bodies during cell division in PANC-1 cells. In particular, spindle bending was most significantly increased. Expression of EGFP-tagged Δ3-tubulin driven by the endogenous promoter of human TUBA1B also deformed and misoriented spindle bodies. Spindle bending and condensation defects were significantly observed by EGFP-Δ3-tubulin expression. Furthermore, EGFP-Δ3-tubulin expression increased the nuclear size in a dose-dependent manner of EGFP-Δ3-tubulin expression. The expression of EGFP-Δ3-tubulin tended to slow down cell proliferation. Taken together, our results demonstrate that Δ3-tubulin affects the spindle integrity and cell division.
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Metadata
Title
Δ3-tubulin impairs mitotic spindle morphology and increases nuclear size in pancreatic cancer cells
Authors
Kenta Baba
Kenichiro Uemura
Ryota Nakazato
Faryal Ijaz
Shinya Takahashi
Koji Ikegami
Publication date
06-11-2023
Publisher
Springer Nature Singapore
Published in
Medical Molecular Morphology / Issue 1/2024
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI
https://doi.org/10.1007/s00795-023-00373-w

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