Selected Golgi-Localized Proteins and Carcinogenesis: What Do We Know?

Donizy, Piotr; Marczuk, Jakub

doi:10.1007/978-3-030-23173-6_20

Cited by 7 publications

(11 citation statements)

References 175 publications

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“…The Golgi complex is part of the cytoplasmic endomembrane system, which is normally found adjacent to the nucleus . Transmission electron microscopy analysis revealed that the Golgi forms stacks consisting of eight-storey cisterns placed parallel to each other (Donizy and Marczuk, 2019). The Golgi complex is divided into three compartments: (1) the cis-Golgi network (near the ER and receiving its output), (2) the middle part, and (3) the trans-Golgi network (TGN, near the PM that sends vesicle-dependent and vesicle-independent molecules to different destinations) (Witkos and Lowe, 2016).…”

Section: Endoplasmic Reticulum-trans Golgi Networkmentioning

confidence: 99%

Relevance of Membrane Contact Sites in Cancer Progression

Gil-Hernández

Arroyo-Campuzano

Simoni‐Nieves

et al. 2021

Front. Cell Dev. Biol.

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Membrane contact sites (MCS) are typically defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins. The study of MCS is considered as an emergent field that shows how crucial organelle interactions are in cell physiology. MCS regulate a myriad of physiological processes such as apoptosis, calcium, and lipid signaling, just to name a few. The membranal interactions between the endoplasmic reticulum (ER)–mitochondria, the ER–plasma membrane, and the vesicular traffic have received special attention in recent years, particularly in cancer research, in which it has been proposed that MCS regulate tumor metabolism and fate, contributing to their progression. However, as the therapeutic or diagnostic potential of MCS has not been fully revisited, in this review, we provide recent information on MCS relevance on calcium and lipid signaling in cancer cells and on its role in tumor progression. We also describe some proteins associated with MCS, like CERT, STIM1, VDAC, and Orai, that impact on cancer progression and that could be a possible diagnostic marker. Overall, these information might contribute to the understanding of the complex biology of cancer cells.

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Section: Endoplasmic Reticulum-trans Golgi Networkmentioning

confidence: 99%

Relevance of Membrane Contact Sites in Cancer Progression

Gil-Hernández

Arroyo-Campuzano

Simoni‐Nieves

et al. 2021

Front. Cell Dev. Biol.

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“…Mitosis is the most prevalent process that requires Golgi fragmentation that in this case is required for the division of the Golgi into two daughter cells. Other processes that may involve Golgi fragmentation, mostly partial, include migration, apoptosis, neurological disorders and cancers (Caracci et al, 2019;Donizy and Marczuk, 2019;Farhan and Hsu, 2016). The mechanism that During interphase the Golgi is organized in stacks, while GM130 is found in between these stacks.…”

Section: Discussionmentioning

confidence: 99%

Mitotic HOOK3 phosphorylation by ERK1c drives microtubule-dependent Golgi destabilization and fragmentation

et al. 2021

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ERK1c is an alternatively spliced isoform of ERK1 that specifically regulates mitotic Golgi fragmentation, which allows division of the Golgi during mitosis. We have previously shown that ERK1c translocates to the Golgi during mitosis where it is activated by a resident MEK1b to induce Golgi fragmentation. However, the mechanism of ERK1c functions in the Golgi remained obscure. Here, we searched for ERK1c substrates and identified HOOK3 as a mediator of ERK1cinduced mitotic Golgi fragmentation, which requires a second phosphorylation by AuroraA for its function. In cycling cells, HOOK3 interacts with microtubules (MTs) and links them to the Golgi. Early in mitosis, HOOK3 is phosphorylated by ERK1c and later by AuroraA, resulting in HOOK3 detachment from the MTs, and elevated interaction with GM130. This detachment modulates Golgi stability and allows fragmentation of the Golgi. This study demonstrates a novel mechanism of Golgi apparatus destabilization early in mitosis to allow mitotic progression.

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“…Our findings also highlight the need of considering possible functional heterogeneity in the effects of overexpressed GOLPH3 in different cancer cell lines. 1), undergoes N-glycosylation in the Golgi apparatus, including terminal sialylation and fucosylation (2). Monomeric EGFR reaches the cell surface (3).…”

Section: Discussionmentioning

confidence: 99%

“…The Golgi apparatus is a key subcellular compartment of the secretory pathway involved in multiple functions, such as posttranslational modifications and distribution of glycolipids and glycoproteins [1]. Increasing evidence indicates that the Golgi apparatus is also involved in pathogenic processes, such as in carcinogenesis, although its precise role is unclear [2]. Intriguingly, overexpression of Golgi proteins, such as GOLPH3, have been found in different types of tumors, but the molecular mechanisms by which the levels of these proteins are connected to tumorigenesis are not well understood [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Increasing evidence indicates that the Golgi apparatus is also involved in pathogenic processes, such as in carcinogenesis, although its precise role is unclear [2]. Intriguingly, overexpression of Golgi proteins, such as GOLPH3, have been found in different types of tumors, but the molecular mechanisms by which the levels of these proteins are connected to tumorigenesis are not well understood [2,3]. Remarkably, in different types of cancer, increasing levels of GOLPH3 are correlated with poor survival, being proposed as a biomarker of malignant progression [4,5].…”

Section: Introductionmentioning

confidence: 99%

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GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Arriagada

Cavieres

Luchsinger

et al. 2020

IJMS

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Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.

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Selected Golgi-Localized Proteins and Carcinogenesis: What Do We Know?

Cited by 7 publications

References 175 publications

Relevance of Membrane Contact Sites in Cancer Progression

Relevance of Membrane Contact Sites in Cancer Progression

Mitotic HOOK3 phosphorylation by ERK1c drives microtubule-dependent Golgi destabilization and fragmentation

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

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