Adaptation of the Golgi Apparatus in Cancer Cell Invasion and Metastasis

Bui, Sarah; Mejia, Isabel; Díaz, Begoña; Wang, Yanzhuang

doi:10.3389/fcell.2021.806482

Cited by 37 publications

(41 citation statements)

References 196 publications

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“…Hence, we could speculate that constitutive Golgi unlinking could be a favorable condition for tumorigenesis. Of note, there are reports suggesting that the GC is unlinked in certain cancer cells (Bui et al, 2021) and that GC fragmentation may sustain cell survival and resistance to DNA-damaging agents, limiting the efficacy of chemotherapy (Farber-Katz et al, 2014). Nevertheless, despite the important potential pathological implications of the functional connection between Golgi inheritance and cell division, this topic has been showing a steady decline in interest over the last 15 years, as evidenced by the PubMed search for the words "Golgi" and "mitosis".…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we hope for a renewed interest of the scientific community in the investigation of the basic mechanisms and regulation of mitotic Golgi disassembly, its connections with the control of mitotic processes and the effects of alterations of Golgi inheritance on genomic stability. In addition, more systematic studies of the structure and function of the GC in patient tissues and patient-derived cells are much needed for a better understanding of the link between GC and cancer (Bui et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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Structural Organization and Function of the Golgi Ribbon During Cell Division

Ayala

Colanzi²

2022

Front. Cell Dev. Biol.

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The Golgi complex has a central role in the secretory traffic. In vertebrate cells it is generally organized in polarized stacks of cisternae that are laterally connected by membranous tubules, forming a structure known as Golgi ribbon. The steady state ribbon arrangement results from a dynamic equilibrium between formation and cleavage of the membrane tubules connecting the stacks. This balance is of great physiological relevance as the unlinking of the ribbon during G2 is required for mitotic entry. A block of this process induces a potent G2 arrest of the cell cycle, indicating that a mitotic “Golgi checkpoint” controls the correct pre-mitotic segregation of the Golgi ribbon. Then, after mitosis onset, the Golgi stacks undergo an extensive disassembly, which is necessary for proper spindle formation. Notably, several Golgi-associated proteins acquire new roles in spindle formation and mitotic progression during mitosis. Here we summarize the current knowledge about the basic principle of the Golgi architecture and its functional relationship with cell division to highlight crucial aspects that need to be addressed to help us understand the physiological significance of the ribbon and the pathological implications of alterations of this organization.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structural Organization and Function of the Golgi Ribbon During Cell Division

Ayala

Colanzi²

2022

Front. Cell Dev. Biol.

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“…Golgi fragmentation occurs in pathological situations, such as when apoptosis is activated and when vesicular secretory trafficking is perturbed [ 21 , 47 , 48 , 49 , 50 , 51 , 52 ]. Furthermore, several evidences show that the Golgi apparatus plays a key role in sensing and integrating external and intracellular cues to promote cellular homeostasis [ 53 , 54 ]. Similarly, from what we observed, mice lacking the fukutin gene (Fktn), the causative gene of Fukuyama muscular dystrophy, show myocyte contractile dysfunction and a disordered Golgi network [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

The Capillary Morphogenesis Gene 2 Triggers the Intracellular Hallmarks of Collagen VI-Related Muscular Dystrophy

Castroflorio

Berná

López-Márquez

et al. 2022

IJMS

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Collagen VI-related disorders (COL6-RD) represent a severe form of congenital disease for which there is no treatment. Dominant-negative pathogenic variants in the genes encoding α chains of collagen VI are the main cause of COL6-RD. Here we report that patient-derived fibroblasts carrying a common single nucleotide variant mutation are unable to build the extracellular collagen VI network. This correlates with the intracellular accumulation of endosomes and lysosomes triggered by the increased phosphorylation of the collagen VI receptor CMG2. Notably, using a CRISPR-Cas9 gene-editing tool to silence the dominant-negative mutation in patients’ cells, we rescued the normal extracellular collagen VI network, CMG2 phosphorylation levels, and the accumulation of endosomes and lysosomes. Our findings reveal an unanticipated role of CMG2 in regulating endosomal and lysosomal homeostasis and suggest that mutated collagen VI dysregulates the intracellular environment in fibroblasts in collagen VI-related muscular dystrophy.

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“…Changes in microtubule dynamics and dispersal of Golgi have been frequently associated with cancer progression (Bui et al, 2021; Petrosyan, 2015). Despite being thoroughly studied, the exact role of Golgi in cancer progression remains inconclusive.…”

Section: Discussionmentioning

confidence: 99%

DNA damage leads to microtubule stabilisation through an increase in Golgi-derived microtubules

Venkataravi

Lahiri

2022

Preprint

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The site of nucleation strongly determines microtubule organisation and dynamics. The centrosome is a primary site for microtubule nucleation and organisation in most animal cells. In recent years, the Golgi apparatus has emerged as a site of microtubule nucleation and stabilisation. The microtubules originating from Golgi are essential for maintaining Golgi integrity post-Golgi trafficking, establishing cell polarity and enabling cell motility. Although the mechanism of nucleation and functional relevance of the Golgi-nucleated microtubule is well established, its regulation is not well studied. In this study, we report that DNA damage leads to aberrant Golgi structure and function accompanied by reorganisation of the microtubule network. Characterisation of microtubule dynamics post DNA damage showed the presence of a stable pool of microtubules resistant to depolymerisation by nocodazole and enriched in acetylated tubulin. Investigation of the functional association between Golgi dispersal and microtubule stability revealed that the Golgi elements were distributed along the acetylated microtubules. Microtubule regrowth assays showed an increase in Golgi-derived microtubule post DNA damage. Interestingly, reversal of Golgi dispersal reduces microtubule stabilisation. Altered intracellular trafficking resulting in mislocalisation of cell-cell junction proteins was observed post DNA damage. We propose that the increase in stable microtubules deregulates intracellular trafficking, resulting in cell polarity changes. This study would thus be the first to demonstrate the link between Golgi dispersal and microtubule reorganisation orchestrating changes in cell polarity.

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Adaptation of the Golgi Apparatus in Cancer Cell Invasion and Metastasis

Cited by 37 publications

References 196 publications

Structural Organization and Function of the Golgi Ribbon During Cell Division

Structural Organization and Function of the Golgi Ribbon During Cell Division

The Capillary Morphogenesis Gene 2 Triggers the Intracellular Hallmarks of Collagen VI-Related Muscular Dystrophy

DNA damage leads to microtubule stabilisation through an increase in Golgi-derived microtubules

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