Tubulin Tyrosine Ligase Like 4 (TTLL4) overexpression in breast cancer cells is associated with brain metastasis and alters exosome biogenesis

Arnold, Julia; Schattschneider, Juliana; Schlüter, Hartmut; Schweizer, Michaela; Nalaskowski, Marcus M.; Oliveira‐Ferrer, Leticia; Windhorst, Sabine

doi:10.1186/s13046-020-01712-w

Cited by 29 publications

(17 citation statements)

References 39 publications

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“…In a cancer cell context, altered polyglutamylation is linked to tumorigenesis and resistance to drug targeting MTs. A recent study showed that tubulin tyrosine ligase-like 4 (TTLL4) overexpression in breast cancer cells is associated with increased polyglutamylation of TubB, alteration of exosome homeostasis, and brain metastasis [ 90 ]. In pancreatic cancer cells, genetic downregulation of TTLL4 attenuates cell proliferation [ 91 ].…”

Section: The Tubulin Code and Its Associated Enzymes In Cancermentioning

confidence: 99%

The Tubulin Code and Tubulin-Modifying Enzymes in Autophagy and Cancer

Trisciuoglio

Degrassi

2021

Cancers

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Microtubules are tubulin polymers that constitute the structure of eukaryotic cells. They control different cell functions that are often deregulated in cancer, such as cell shape, cell motility and the intracellular movement of organelles. Here, we focus on the crucial role of tubulin modifications in determining different cancer characteristics, including metastatic cell migration and therapy resistance. We also discuss the influence of microtubule modifications on the autophagic process—the cellular degradation pathway that influences cancer growth. We discuss findings showing that inducing microtubule modifications can be used as a means to kill cancer cells by inhibiting autophagy.

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Section: The Tubulin Code and Its Associated Enzymes In Cancermentioning

confidence: 99%

The Tubulin Code and Tubulin-Modifying Enzymes in Autophagy and Cancer

Trisciuoglio

Degrassi

2021

Cancers

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“…Additionally, glutamylation was also associated with cancer. A study screened for genes with correlation for brain metastasis by microarray and showed that TTLL4, a tubulin glutamylase enzyme, overexpression in breast cancer cells is associated with brain metastasis ( Arnold et al, 2020 ).…”

Section: Posttranslational Modification Enzymes With a Role In Ciliog...mentioning

confidence: 99%

Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna

Rocha

Prinos

2022

Front. Cell. Neurosci.

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Primary cilia direct cellular signaling events during brain development and neuronal differentiation. The primary cilium is a dynamic organelle formed in a multistep process termed ciliogenesis that is tightly coordinated with the cell cycle. Genetic alterations, such as ciliary gene mutations, and epigenetic alterations, such as post-translational modifications and RNA processing of cilia related factors, give rise to human neuronal disorders and brain tumors such as glioblastoma and medulloblastoma. This review discusses the important role of genetics/epigenetics, as well as RNA processing and post-translational modifications in primary cilia function during brain development and cancer formation. We summarize mouse and human studies of ciliogenesis and primary cilia activity in the brain, and detail how cilia maintain neuronal progenitor populations and coordinate neuronal differentiation during development, as well as how cilia control different signaling pathways such as WNT, Sonic Hedgehog (SHH) and PDGF that are critical for neurogenesis. Moreover, we describe how post-translational modifications alter cilia formation and activity during development and carcinogenesis, and the impact of missplicing of ciliary genes leading to ciliopathies and cell cycle alterations. Finally, cilia genetic and epigenetic studies bring to light cellular and molecular mechanisms that underlie neurodevelopmental disorders and brain tumors.

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“…57,58 TTLL4, a cytoskeleton-associated protein, mediates β-tubulin glutamylation and alters the characteristics of exosomes, which increases the adhesion and permeability of breast cancer cells to BBB endothelial cells and increase the chance of brain metastasis. 59…”

Section: Biomaterials Science Reviewmentioning

confidence: 99%