Alterations of Golgi Structural Proteins and Glycosylation Defects in Cancer

The biosynthetic transport route that constitutes the secretory pathway plays a fundamental role in the cell, providing to the synthesis and transport of around one third of human proteins and most lipids. Signaling molecules within autoregulatory circuits on the intracellular membranes of the secretory pathway regulate these processes, especially at the level of the Golgi complex. Indeed, cancer cells can hijack several of these signaling molecules, and therefore also the underlying regulated processes, to bolster their growth or gain more aggressive phenotypes. Here, we review the most important autoregulatory circuits acting on the Golgi, emphasizing the role of specific signaling molecules in cancer. In fact, we propose to draw awareness to highlight the Golgi-localized regulatory systems as potential targets in cancer therapy.

Section: Discussionmentioning

confidence: 99%

Endogenous and Exogenous Regulatory Signaling in the Secretory Pathway: Role of Golgi Signaling Molecules in Cancer

Giudice

Luca

Parizadeh

et al. 2022

“…Accumulating evidence has shown that a proper Golgi structure is essential for its suitable functions, especially glycosylation (X. Zhang, 2021 ). Notably, altered glycosylation of cell surface proteins and lipids is a well-accepted cancer hallmark ( Martins et al, 2021 ; Zhang, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“… Zhang, 2021 ). Notably, altered glycosylation of cell surface proteins and lipids is a well-accepted cancer hallmark ( Martins et al, 2021 ; Zhang, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

Jiang

Ouyang

Zhang

et al. 2022

The Golgi apparatus (GA) is a cellular organelle that participates in the packaging, modification, and transport of proteins and lipids from the endoplasmic reticulum to be further fabricated before being presented to other cellular components. Recent studies have demonstrated that GA facilitates numerous cellular processes in cancer development. Therefore, this study aimed to establish a novel lung adenocarcinoma (LUAD) risk evaluation model based on GA gene signatures. In this study, we used TCGA-LUAD (n = 500) as the training cohort and GSE50081 (n = 127), GSE68465 (442), and GSE72094 (398) as the validation cohorts. Two immunotherapy datasets (GSE135222 and GSE126044) were also obtained from a previous study. Based on machine algorithms and bioinformatics methods, a GA gene-related risk score (GARS) was established. We found that the GARS independently predicted the prognosis of LUAD patients and remained effective across stages IA to IIIA. Then, we identified that the GARS was highly correlated with mutations in P53 and TTN. Further, this study identified that GARS is related to multiple immune microenvironmental characteristics. Furthermore, we investigated GSE135222 and GSE126044 and found that a lower GARS may be indicative of an improved therapeutic effect of PD-1/PD-L1 therapy. We also found that high GARS may lead to a better response to multiple anticancer drugs. Finally, we established a nomogram to better guide clinical application. To our knowledge, this is the first study to demonstrate a novel GA signature-based risk score formula to predict clinical prognosis and guide the treatment of LUAD patients.

“…In tissue culture, the Golgi ribbon is intact in many cancer cell lines, but it undergoes morphological change upon the induction of epithelial-to-mesenchymal transition (EMT) or migration (Bisel et al, 2008b). Golgi fragmentation is often seen in various tumor tissue types from patients (Maldonado et al, 1966;Tani et al, 1975;Castejón, 1999;Kellokumpu et al, 2002;Sano et al, 2002;Zhang, 2021). Frozen tissue sections showed intact Golgi structure in normal colon epithelial cells, in contrast to small punctate Golgi structure found in cancerous colon epithelium FIGURE 1 | Golgi morphology in cancer cell lines.…”

Section: Golgi Fragmentation In Cancermentioning

confidence: 99%

“…While most cancer cell lines in culture have an intact Golgi ribbon, future research should investigate the Golgi structure in 3D models that better represent tumor microenvironment and cancer cell progression. Our speculation that Golgi alteration facilitates cancer biogenesis is based on the following reasons: 1) The Golgi undergoes morphological change in tissue culture upon the induction of EMT (Tan et al, 2017) or migration (Bisel et al, 2008b); 2) Golgi fragmentation is often seen in cancer tissues (Maldonado et al, 1966;Tani et al, 1975;Kellokumpu et al, 2002;Sano et al, 2002;Petrosyan, 2015;Zhang, 2021); 3) Alteration of Golgi functions such as glycosylation is a hallmark of cancer cells (Zhang, 2021). 4) While an organized Golgi structure is required for accurate protein glycosylation and sorting, our study revealed that Golgi fragmentation accelerates protein trafficking and cell proliferation (Xiang et al, 2013;Zhang and Wang, 2016;Bekier et al, 2017).…”

Section: Future Direction and Concluding Remarksmentioning

confidence: 99%

Adaptation of the Golgi Apparatus in Cancer Cell Invasion and Metastasis

Bui

Mejia

Díaz

et al. 2021

The Golgi apparatus plays a central role in normal cell physiology by promoting cell survival, facilitating proliferation, and enabling cell-cell communication and migration. These roles are partially mediated by well-known Golgi functions, including post-translational modifications, lipid biosynthesis, intracellular trafficking, and protein secretion. In addition, accumulating evidence indicates that the Golgi plays a critical role in sensing and integrating external and internal cues to promote cellular homeostasis. Indeed, the unique structure of the mammalian Golgi can be fine-tuned to adapt different Golgi functions to specific cellular needs. This is particularly relevant in the context of cancer, where unrestrained proliferation and aberrant survival and migration increase the demands in Golgi functions, as well as the need for Golgi-dependent sensing and adaptation to intrinsic and extrinsic stressors. Here, we review and discuss current understanding of how the structure and function of the Golgi apparatus is influenced by oncogenic transformation, and how this adaptation may facilitate cancer cell invasion and metastasis.