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KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution.

Overview

Authors: Taylor V Joseph1, Andrea B Pham1, Kiara E Bornes1, Razan H Hammad2, Chelsea A Rousseve‐Ross1, Thomas M Huckaba2, Terry J Watt1, Tasha B Toro1
  1. Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
  2. Department of Biology, Xavier University of Louisiana, New Orleans, LA, USA
Institutions: Xavier University of Louisiana (United States)
Journal: FEBS open bio, pages 10.1002/2211-5463.70302
Dates: received 9 February 2026; accepted 23 June 2026; published online 25 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/2211-5463.70302 · PMID 42798205 · PMCID PMC13615371 · OpenAlex W7214484332
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), cellular / molecular (subfield)
Methods: Statistics, Preprocessing, Machine learning
Keywords: acetylation, actin, cell morphology, cell motility, histone deacetylase 6, RNA‐seq
Topic: Histone Deacetylase Inhibitors Research (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Army Research Laboratory (W911NF-15-1-0059); National Science Foundation (1817358, 2309093); NIH HHS (P20GM103424, RL5GM118966, U54MD007595); Louisiana Cancer Research Center
Citations: not cited yet (Europe PMC); 76 references in the paper

Abstract

Lysine deacetylase 6 (KDAC6 or HDAC6) has been associated with cell motility and deacetylation of cytoskeleton‐related proteins. KDAC6 is the only human KDAC having three identified major domains, including two catalytic domains (CD). Defining the roles of KDAC6 in cell motility has been constrained by limited understanding of domain‐specific contributions. Live and fixed cell imaging was used to characterize the effects of KDAC6 on F‐actin distribution, cell morphology, and cell motility of genetically modified HT1080 cells containing KDAC6 with an inactivated CD or knockout. CD1 inactivation resulted in cells that migrated faster and had more concentrated cortical F‐actin at the leading edge. Conversely, inactivation of CD2 resulted in slower migration, depleted cortical F‐actin, more stress fibers with poor alignment, and larger, flatter cells. Loss of both CD1 and CD2 activity in the knockout cell line resulted in phenotypes that were most similar to wild‐type cells. Hyperacetylation of α‐tubulin alone was insufficient to explain the observed phenotypes of the cell line with inactive CD2, as the knockout cell line had similar hyperacetylation but lacked most of the phenotypic changes. Altered gene expression implicated actin‐associated proteins as mediators of phenotypic effects. Although the cell lines exhibited variation in localization of putative KDAC6 targets cortactin and HSP90, these variations did not correlate with the observed phenotypes. Inactivation of CD2 resulted in more focal adhesions formed throughout cells, correlating with more stress fibers and reduced motility. Collectively, these results establish that each CD of KDAC6 has a distinctive and opposing role in F‐actin regulation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

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Data accessibility

The data that support the findings of this study that are not included in their entirety in this report are openly available in Gene Expression Omnibus at www.ncbi.nlm.nih.gov/geo/, reference numbers GSE228549 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228549), GSE302260 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302260), and GSE302329 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302329), and in Open Science Framework at 10.17605/OSF.IO/Y6DSA (https://doi.org/10.17605/OSF.IO/Y6DSA) (fixed cell fluorescence microscopy), 10.17605/OSF.IO/D9HSK (https://doi.org/10.17605/OSF.IO/D9HSK) (flow cytometry), and 10.17605/OSF.IO/S48WE (https://doi.org/10.17605/OSF.IO/S48WE) (live cell microscopy).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, pages, dates, 8 authors, 6 keywords, 4 funders, 76 references.

Cite

This paper

Joseph, T. V., Pham, A. B., Bornes, K. E., Hammad, R. H., Rousseve‐Ross, C. A., Huckaba, T. M., Watt, T. J., & Toro, T. B. (2026). KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution. FEBS open bio, 10.1002/2211-5463.70302. https://doi.org/10.1002/2211-5463.70302

BibTeX

@article{joseph2026kdac6,
author = {Joseph, Taylor V and Pham, Andrea B and Bornes, Kiara E and Hammad, Razan H and Rousseve‐Ross, Chelsea A and Huckaba, Thomas M and Watt, Terry J and Toro, Tasha B},
title = {{KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution}},
journal = {FEBS open bio},
year = {2026},
month = sep,
pages = {10.1002/2211--5463.70302},
publisher = {Wiley},
issn = {2211-5463},
doi = {10.1002/2211-5463.70302},
url = {https://doi.org/10.1002/2211-5463.70302},
pmid = {42798205},
pmcid = {PMC13615371}
}

RIS

TY - JOUR
AU - Joseph, Taylor V
AU - Pham, Andrea B
AU - Bornes, Kiara E
AU - Hammad, Razan H
AU - Rousseve‐Ross, Chelsea A
AU - Huckaba, Thomas M
AU - Watt, Terry J
AU - Toro, Tasha B
TI - KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution
T2 - FEBS open bio
J2 - FEBS Open Bio
PY - 2026
DA - 2026/09/25
SP - 10.1002/2211
EP - 5463.70302
SN - 2211-5463
PB - Wiley
DO - 10.1002/2211-5463.70302
UR - https://doi.org/10.1002/2211-5463.70302
LA - en
ER -

CSL-JSON

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"issued": {
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