Targeting the Lysosomal Degradation of Rab22a‐NeoF1 Fusion Protein for Osteosarcoma Lung Metastasis

Zeng, Cuiling; Zhong, Li; Liu, Wenqiang; Yu, Xin-Hao; Wang, Xin; Zhang, Ruhua; Kang, Tiebang; Liao, Dan

doi:10.1002/advs.202205483

Cited by 9 publications

(4 citation statements)

References 58 publications

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“…By precisely identifying and engaging with these distinct cellular markers or pathways, treatments can attain a heightened level of selectivity. This, in turn, can amplify therapeutic efficacy while concurrently diminishing inadvertent harm to healthy cells and tissues [ 53 , 97 , 98 , 99 ]. Yet, it is essential to recognize that these targeted interventions, like all therapeutic approaches, have inherent challenges.…”

Section: Resultsmentioning

confidence: 99%

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Luo,

Sun,

Tan

et al. 2023

Pharmaceutics

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Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

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Section: Resultsmentioning

confidence: 99%

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Luo,

Sun,

Tan

et al. 2023

Pharmaceutics

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“…The other eight studies interfered with communication mediators using other medicines, such as cancer susceptibility 15 (CASC15) or KLF3 antisense RNA 1 (KLF3-AS1) [129][130], programmed cell death 4 (PDCD4) [131][132], autophagy-related gene 5 (ATG5) [133] [134], and Rab22a-NeoF1 fusion protein [135] [136]. Other medicines interfered with Ras-associated binding 14 (RAB14), extracellular signal-regulated kinase-1/2 (ERK1/2) signalling pathway, oncogenic autophagy, and M2 with Arginylglycylaspartic acid (RGD) peptide internalisation in STAT3 by suppressing miR-338-3p; miR-208a EV; BMSC-derived EV; and protein tyrosine kinase-2 (PYK2) and Ras homolog family member A (RhoA); respectively.…”

Section: Interfere Communication Mediators' Therapiesmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

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“…As a newly discovered selective autophagy receptor, NDP52 is mainly localised on the mitochondrial outer membrane and regulates mitophagy mediated by the PINK1/ Parkin pathway (Kataura et al, 2022;Lazarou et al, 2015). It has been reported that cysteine residues of NDP52 can form disulphide bonds under the oxidation of mitochondrial respiratory chain complexes I and III, which then recruit Parkin to the mitochondria and interact with PINK1, thereby inducing mitophagy initiation (Zeng et al, 2023). Park et al (2022) revealed that a high-fat diet promoted the upregulation of NDP52 expression through activation of the transcription factor TFEB, which further accelerated the activation of PINK1/Parkin-mediated mitophagy.…”

Section: Introductionmentioning

confidence: 99%

NDP52 SUMOylation contributes to low‐dose X‐rays‐induced cardiac hypertrophy through PINK1/Parkin‐mediated mitophagy via MUL1/SUMO2 signalling

Gao,

Wang,

Tang

et al. 2023

Journal Cellular Physiology

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Radiation‐induced heart damage caused by low‐dose X‐rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL‐IN‐1 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage. Isobaric tags for relative and absolute quantification‐based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low‐dose X‐rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co‐IP coupled with LC–MS/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2‐mediated SUMOylation of NDP52. The point mutation plasmid NDP52K262R inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52K262R inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52K262R impaired the recruitment of mitochondria to the autophagic pathway through EEA1/RAB11 and ATG3, ATG5, ATG16L1 and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1‐mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low‐dose X‐ray‐induced cardiac hypertrophy. Two hundred sixty‐second lysine of NDP52 is identified as a key SUMOylation site for low‐dose X‐ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low‐dose X‐rays.

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Targeting the Lysosomal Degradation of Rab22a‐NeoF1 Fusion Protein for Osteosarcoma Lung Metastasis

Cited by 9 publications

References 58 publications

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

NDP52 SUMOylation contributes to low‐dose X‐rays‐induced cardiac hypertrophy through PINK1/Parkin‐mediated mitophagy via MUL1/SUMO2 signalling

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