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Rios Garcia, M. ; Meissburger, B.* ; Chan, J. ; de Guia, R.M.* ; Mattijssen, F. ; Roessler, S.* ; Birkenfeld, A.L. ; Raschzok, N.* ; Riols, F. ; Tokarz, J. ; Giroud, M. ; Gil Lozano, M. ; Hartleben, G. ; Nawroth, P.P. ; Haid, M. ; López, M.* ; Herzig, S. ; Berriel Diaz, M.

Trip13 depletion in liver cancer induces a lipogenic response contributing to plin2-dependent mitotic cell death.

Adv. Sci. 9:e2104291 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Aberrant energy metabolism and cell cycle regulation both critically contribute to malignant cell growth and both processes represent targets for anticancer therapy. It is shown here that depletion of the AAA+-ATPase thyroid hormone receptor interacting protein 13 (Trip13) results in mitotic cell death through a combined mechanism linking lipid metabolism to aberrant mitosis. Diminished Trip13 levels in hepatocellular carcinoma cells result in insulin-receptor-/Akt-pathway-dependent accumulation of lipid droplets, which act as functional acentriolar microtubule organizing centers disturbing mitotic spindle polarity. Specifically, the lipid-droplet-coating protein perilipin 2 (Plin2) is required for multipolar spindle formation, induction of DNA damage, and mitotic cell death. Plin2 expression in different tumor cells confers susceptibility to cell death induced by Trip13 depletion as well as treatment with paclitaxel, a spindle-interfering drug commonly used against different cancers. Thus, assessment of Plin2 levels enables the stratification of tumor responsiveness to mitosis-targeting drugs, including clinically approved paclitaxel and Trip13 inhibitors currently under development.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mtocs ; Plin2 ; Trip13 ; Hepatocellular Carcinoma ; Lipogenesis ; Mitosis ; Spindle Assembly Checkpoint
ISSN (print) / ISBN 2198-3844
e-ISSN 2198-3844
Journal Advanced science
Quellenangaben Volume: 9, Issue: 29, Pages: , Article Number: e2104291 Supplement: ,
Publisher Wiley
Publishing Place Weinheim
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
Institute of Diabetes Research and Metabolic Diseases (IDM)
CF Metabolomics & Proteomics (CF-MPC)
Grants Ministerio de Economía y Competitividad (MINECO) co-funded by FEDER Program of EU
Helmholtz Future Topic AMPro