CRISPR screens and lectin microarrays identify high mannose N-glycan regulators DOI Creative Commons
C. Kimberly Tsui,

Nicholas M. Twells,

Jenni Durieux

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 18, 2024

Abstract Glycans play critical roles in cellular signaling and function. Unlike proteins, glycan structures are not templated from genetic sequences but synthesized by the concerted activity of many genes, making them historically challenging to study. Here, we present a strategy that utilizes CRISPR screens lectin microarrays uncover characterize regulators glycosylation. We applied this approach study regulation high mannose glycans – starting structure all asparagine(N)-linked-glycans. used expanded network genes controlling levels, followed fully measure complex effect select on glycosylation globally. Through this, elucidated how two TM9SF3 CCC control N-glycosylation via regulating Golgi morphology Notably, allows us interrogate function in-depth reveals similar disruption can lead drastically different outcomes. Collectively, work demonstrates generalizable for systematically dissecting regulatory underlying

Language: Английский

Triphenylamine-Naphthalimide-Based “On–Off–On” AIEgen for Imaging Golgi Apparatus and Endoplasmic Reticulum DOI
Prashant Kumar, Tripti Mishra,

Sanyam Sanyam

et al.

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Golgi apparatus (GA) and endoplasmic reticulum (ER) are two of the interesting subcellular organelles that critical for protein synthesis, folding, processing, post-translational modifications, secretion. Consequently, dysregulation in GA ER cross-talk between them implicated numerous diseases including cancer. As a result, simultaneous visualization cancer cells is extremely crucial developing therapeutics. To address this, herein, we have designed synthesized 1,8-napthalimide-based small molecule (AIE-GA-ER) consisting phenylsulfonamide as Golgi-ER homing triphenylamine-napthalimide aggregation-induced emission (AIE) triggering moieties. AIE-GA-ER exhibited remarkable "on-off-on" AIE properties THF/water binary solvent system due to aggregated "on-state" pure THF 80% water THF. Molecular dynamic simulations density functional theory (DFT) calculations underlying mechanism emissive property be interplay intramolecular charge transfer (ICT) stabilization aggregation THF, DMSO, water. efficiently homed into HCT-116 colon within 15-30 min well noncancerous human retinal epithelial pigment (RPE-1) 3 h with minimum toxicity. This AIEgen has potential illuminate simultaneously understand chemical biology their next-generation

Language: Английский

Citations

0
A Golgi apparatus‑related subtype and risk signature predicts prognosis and evaluates immunotherapy response in gastric cancer DOI Creative Commons

Ruyue Chen,

Zengwu Yao,

Lixin Jiang

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Gastric cancer (GC) remains a significant health burden, calling for the discovery of novel biomarkers. Golgi apparatus, crucial cellular organelle involved in tumorigenesis, underexplored GC research. A comprehensive understanding its role and associated mechanisms is urgently needed. Utilizing TCGA-STAD dataset as training cohort GSE84433 validation cohort, we explored potential associations between apparatus-related genes (GARG) clinical risk. We aimed to decipher prognostic significance underlying biological these via consistent clustering, differential expression analysis, enrichment analyses, immune infiltration profiling. To assess relationship risk stratification survival outcomes, drug sensitivity, infiltration, developed Apparatus-Related Risk Signature (GARRS). The reliability GARRS was further corroborated using immunohistochemical staining. Consensus clustering based on 17 GARG identified two patient subgroups, C1 C2, exhibiting survival, scores, cell infiltration. Cox-Lasso regression accurately stratifying patients into high- low-risk groups. GARRS' validity confirmed set Our findings underline apparatus' microenvironment utility predicting outcomes. This study underscores association apparatus subtypes immunotumor microenvironment. GARRS, validated prognostic, sensitivity predictive abilities, offers new insights gastric treatment strategies.

Language: Английский

Citations

0
Subcellular Organelle Targeting as a Novel Approach to Combat Tumor Metastasis DOI Creative Commons
Zefan Liu, Yang Liu, Xin Kang

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 198 - 198

Published: Feb. 5, 2025

Tumor metastasis, the spread of cancer cells from primary site to distant organs, remains a formidable challenge in oncology. Central this process is involvement subcellular organelles, which undergo significant functional and structural changes during metastasis. Targeting these specific organelles offers promising avenue for enhanced drug delivery metastasis therapeutic efficacy. This precision increases potency reduces potential off-target effects. Moreover, by understanding role each organelle treatments can be designed disrupt metastatic at multiple stages, cell migration establishment secondary tumors. review delves deeply into tumor processes their connection with organelles. In order target biomembranes, cell-penetrating peptides, localization signal aptamers, small molecules, various other strategies have been developed. review, we will elucidate targeting look forward prospects domain.

Language: Английский

Citations

0
Unveiling HER2 immunoexpression in canine hepatoid gland neoplasms: clinicopathological and morphological associations DOI Creative Commons
Hassadin BOONSRIROJ, Sahatchai Tangtrongsup, Jirapat Arunorat

et al.

International Journal of Veterinary Science and Medicine, Journal Year: 2025, Volume and Issue: 13(1), P. 1 - 12

Published: April 24, 2025

Canine hepatoid gland neoplasms (HGNs) are significant clinical concerns due to their high prevalence and diverse biological behaviour. Human epidermal growth factor receptor 2 (HER2), a tyrosine kinase implicated in various aspects of tumorigenesis, has been extensively studied human animal but remains unexplored HGNs. This study aimed assess HER2 immunoexpression canine HGNs its association with clinicopathological morphological features. A total 61 formalin-fixed paraffin-embedded samples, including normal glands (n = 10), adenomas (HGAs, n 20), epitheliomas (HGEs, 16), carcinomas (HGCs, 15), were analysed using immunohistochemistry. expression was scored based on percentage positivity staining intensity. HER2-positive detected 50% HGEs (score + ) 73.3% HGCs, 36.4% cases scoring 3 . In contrast, all HGAs tissues HER2-immunonegative. Statistical analysis revealed differences among neoplastic (p < 0.001). Only significantly associated tissue invasion 0.007), mitotic count 0.033), nuclear pleomorphism 0.007). These findings suggest that may play role the progression malignant HGNs, particularly HGCs. preliminary highlights potential as diagnostic marker emphasizes need for further investigation into prognostic value HER2-targeted therapy

Language: Английский

Citations

0
Golgi’s Role in the Development of Possible New Therapies in Cancer DOI Creative Commons

Dragos-Bogdan Vlad,

David-Ioan Dumitrascu, A Dumitraşcu

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(11), P. 1499 - 1499

Published: May 29, 2023

The Golgi apparatus is an important organelle found in most eukaryotic cells. It plays a vital role the processing and sorting of proteins, lipids other cellular components for delivery to their appropriate destinations within cell or secretion outside cell. complex also regulation protein trafficking, post-translational modifications, which are significant development progression cancer. Abnormalities this have been observed various types cancer, although research into chemotherapies that target still its early stages. There few promising approaches being investigated: (1) Targeting stimulator interferon genes protein: STING pathway senses cytosolic DNA activates several signaling events. regulated by numerous modifications relies heavily on vesicular trafficking. Based some observations state decreased expression present cancer cells, agonists developed currently tested clinical trials, showing encouraging results. (2) glycosylation: Altered glycosylation, refers changes carbohydrate molecules attached proteins common feature there methods thwart process. For example, inhibitors glycosylation enzymes shown reduce tumor growth metastasis preclinical models (3) trafficking: responsible trafficking cell, disrupting process may be potential therapeutic approach unconventional occurs response stress does not require involvement organelles. P53 frequently altered gene dysregulating normal damage. mutant p53 drives indirectly upregulation reassembly-stacking 55kDa (GRASP55). Through inhibition models, reduction tumoral metastatic capacity obtained successfully. This review supports hypothesis cytostatic treatment, considering molecular mechanisms neoplastic

Language: Английский

Citations

10
ERK activation by Rab2B in the early secretory pathway impacts the ERGIC-Golgi interface DOI

Ellen J. Tisdale,

Cristina R. Artalejo

Cellular Signalling, Journal Year: 2025, Volume and Issue: 130, P. 111710 - 111710

Published: March 2, 2025

Language: Английский

Citations

0
A Golgi apparatus-related signature predicts the immune microenvironment and prognosis of gastric cancer DOI

Changlei Wu,

Liang Sun, Wenjie Zhu

et al.

Genes and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

Citations

0
A ratiometric fluorescent probe for single and two-photon bioimaging of hydrogen peroxide in vitro and in vivo DOI

Zhongjiao Feng,

Jiasheng Wu, Weimin Liu

et al.

Sensors and Actuators B Chemical, Journal Year: 2023, Volume and Issue: 384, P. 133668 - 133668

Published: March 13, 2023

Language: Английский

Citations

8
Hypoxia-Responsive Golgi-Targeted Prodrug Assembled with Anthracycline for Improved Antitumor and Antimetastasis Efficacy DOI

Chenqi Guo,

Mengying Wu,

Zhaofei Guo

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(24), P. 24972 - 24987

Published: Dec. 13, 2023

Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified secreted by swollen Golgi apparatus in tumor cells. Thus, complex considered as important target for the remedy of metastasis. Currently, targeting technologies are mostly employed Golgi-specific fluorescent probes diagnosis, but their applications therapy rarely reported. Herein, we proposed a prodrug (INR) that can destroy apparatus, which consisted indomethacin (IMC) moiety retinoic acid (RA), disrupting agent. The linker between IMC RA was designed hypoxia-responsive nitroaromatic structure, ensured release prototype drugs hypoxic microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), anthracycline, to form carrier-free nanoparticle (NP) emulsion-solvent evaporation method. A small amount mPEG2000-DSPE added shield positive charges improve stability obtain PEG-modified (PNP). It proved released cells hypoxia promoted release. destructive effect amplified owing ability IMC, also inhibited protumor COX-2/PGE2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary its pulmonary hepatic molecular therapeutic adapted multifarious drug delivery systems disease models, expanded application tactics treatment.

Language: Английский

Citations

8
Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis DOI Creative Commons
Rakhee Bajaj, B. Leticia Rodriguez, William K. Russell

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 40(13), P. 111429 - 111429

Published: Sept. 1, 2022

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput vitro vivo screens, we have previously established Impad1 as driver lung invasion metastasis. Here elucidate that direct target epithelial microRNAs (miRNAs) miR-200 miR∼96 de-repressed during epithelial-to-mesenchymal transition (EMT); thus, establish mode regulation protein. modulates Golgi apparatus morphology vesicular trafficking through its interaction with protein, Syt11. These changes dynamics alter extracellular matrix tumor microenvironment (TME) to promote Inhibiting or Syt11 disrupts cell secretome, regulates TME, reverses invasive phenotype. This work identifies regulator EMT secretome-mediated progression.

Language: Английский

Citations

8