Golgi Complex: A Signaling Hub in Cancer

Spano, Daniela; Colanzi, Antonino

doi:10.3390/cells11131990

Cited by 15 publications

(18 citation statements)

References 163 publications

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“…Interestingly, the Golgi apparatus and mitochondria have been found to be in close contact through imaging techniques [36] yet the molecular details are unclear. The GC as a central hub coordinates multiple cellular processes, motility, growth, autophagy, apoptosis, inflammation, stress responses, and DNA repair [37]. GC-centered signaling cascades do indeed contribute to cancer.…”

Section: Golgi Complex: Ground Zero For Cancermentioning

confidence: 99%

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Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Gómez¹

2022

Preprint

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The Golgi complex (GC) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GC are implicated in a wide range of neurodegenerative diseases. GC defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GC regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GC during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GC? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GC will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GC in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HADDF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GC.

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Section: Golgi Complex: Ground Zero For Cancermentioning

confidence: 99%

“…GC-centered signaling cascades do indeed contribute to cancer. There are targets on the trans-Golgi and cis-Golgi sides [37]; starting with the trans-Golgi there are targets such as EGFR, mTORC1 that converge on SCAMP3. Wnt/B-catenin, NFκB, IRF, TLR, ERK-MAPK, JNK-MAPK converge on Sef.…”

Section: Golgi Complex: Ground Zero For Cancermentioning

confidence: 99%

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Gómez¹

2022

Preprint

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“…The GA as a central hub coordinates multiple cellular processes, motility, growth, autophagy, apoptosis, inflammation, stress responses, and DNA repair [40]. GA-centered signaling cascades do indeed contribute to cancer.…”

Section: Golgi Apparatus: Ground Zero For Cancermentioning

confidence: 99%

“…GA-centered signaling cascades do indeed contribute to cancer. There are targets on the trans-Golgi and cis-Golgi sides [40]; starting with the trans-Golgi there are targets such as EGFR, mTORC1 that converge on SCAMP3. Wnt/B-catenin, NFκB, IRF, TLR, ERK-MAPK, JNK-MAPK converge on Sef.…”

Section: Golgi Apparatus: Ground Zero For Cancermentioning

confidence: 99%

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Gómez¹

2022

Preprint

View full text Add to dashboard Cite

The Golgi apparatus (GA) dysfunctions in Parkinson’s Disease (PD), neurodevelopmental disorders (NDDs), cancer, and organelle structural biology (OSB) can provide insights into therapeutic targets, gene therapy, and drug design. Primary defects and fragmentation within the GA are implicated in a wide range of neurodegenerative diseases. GA defects typically result in mislocation of proteins, accumulation of undegraded proteins, and impaired glycosylation of proteins. Inhibition of vesicular trafficking by α-synuclein (aSyn) may affect the dopamine-producing neurons and neuromodulators. GA regulates apoptosis during pathological mechanisms of neurological diseases and could provide new avenues in treatments through translation research. PD patients bearing the hereditary E46K disease mutation manifest the clinical picture of parkinsonism. How do we provide high resolution nanoimages of the GA during disease to capture dysfunction? Could we visualize the aSyn traffic jam between vesicles in the organelles ER and GA? OSB is emerging as a field as more technology advances and is more accessible. Structural studies of the GA will advance the field of neurological disease forward with an in depth understanding of dysfunction, fragmentation, and defects. Discoveries of the GA in PD, NDDs, and cancer would break new ground and provide translational medicine data of these diseases. Future research could be visualizing high angle annular dark field-STEM (HAADF-STEM) tomograms, cryogenic electron tomography (cryo-ET), multiplex correlative light and electron microscopy (cryo-CLEM), nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) and using soft X-ray tomography (SXT) and computational reconstruction of the GA.

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“…In addition to these canonical functions, the Golgi apparatus is now recognized as a signaling hub for mediating various cellular processes such as cell growth, mitosis, apoptosis, autophagy, ferroptosis and stress responses [ 4 , 5 , 6 , 7 ]. It has been demonstrated that altered signaling events within the Golgi apparatus contribute to the development of various diseases, including cancer [ 8 , 9 , 10 , 11 ]. These cancer-adapted signaling processes can be viewed as a vulnerability of cancer cells that can be exploited for development of selective anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Golgi-Targeting Anticancer Natural Products

Khine

Sakurai

2023

Cancers

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The Golgi apparatus plays an important role in maintaining cell homeostasis by serving as a biosynthetic center for glycans, lipids and post-translationally modified proteins and as a sorting center for vesicular transport of proteins to specific destinations. Moreover, it provides a signaling hub that facilitates not only membrane trafficking processes but also cellular response pathways to various types of stresses. Altered signaling at the Golgi apparatus has emerged as a key regulator of tumor growth and survival. Among the small molecules that can specifically perturb or modulate Golgi proteins and organization, natural products with anticancer property have been identified as powerful chemical probes in deciphering Golgi-related pathways and, in particular, recently described Golgi stress response pathways. In this review, we highlight a set of Golgi-targeting natural products that enabled the characterization of the Golgi-mediated signaling events leading to cancer cell death and discuss the potential for selectively exploiting these pathways for the development of novel chemotherapeutic agents.

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Golgi Complex: A Signaling Hub in Cancer

Cited by 15 publications

References 163 publications

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Golgi-Targeting Anticancer Natural Products

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