Insight Into the Role of Autophagy in Osteosarcoma and Its Therapeutic Implication

Niu, Jianfang; Yan, Taiqiang; Guo, Wei; Wang, Wei; Zhao, Zhi‐Qing

doi:10.3389/fonc.2019.01232

Cited by 47 publications

(32 citation statements)

References 102 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cancer, autophagy is often used to promote cancer cell survival and sustains chemotherapy and radiotherapy resistance through multiple mechanisms. Autophagy can be a fine balance within a cancer cell–too little autophagy leads to accumulating cytotoxicity, and too much autophagy leads to metabolic depletion and cell death [ 44 , 45 ]. Disrupting this balance has promising implications in novel therapeutic approaches in osteosarcoma, especially by means of overcoming therapy resistance.…”

Section: Autophagymentioning

confidence: 99%

“…In their reviews, Liao et al and Niu et al illustrate the molecular mechanisms of autophagy as it applies to osteosarcoma [ 44 , 45 ]. In summary, autophagy is thoroughly regulated at the molecular level, driven by multiple extracellular activators and intracellular signal transduction pathways.…”

Section: Autophagymentioning

confidence: 99%

“…Hypoxia, growth factors, and extracellular stressors drive such pathways as the PI3K/Akt/mTOR pathway, Ras/Raf, ROS/JNK, and hypoxia-inducible factor-1α (HIF-1α) to activate such proteins as the autophagy-related protein family (ATGs) and the autophagosome-associated protein LC3 to drive the formation of phagophores and autophagosomes. These lysosome derivatives become scavengers for organelles and other damaged components to sustain cellular function [ 44 , 45 ].…”

Section: Autophagymentioning

confidence: 99%

See 2 more Smart Citations

Recent Insights into Therapy Resistance in Osteosarcoma

Prudowsky

Yustein

2020

Cancers

View full text Add to dashboard Cite

Osteosarcoma, the most common bone malignancy of childhood, has been a challenge to treat and cure. Standard chemotherapy regimens work well for many patients, but there remain minimal options for patients with progressive or resistant disease, as clinical trials over recent decades have failed to significantly improve survival. A better understanding of therapy resistance is necessary to improve current treatments and design new strategies for future treatment options. In this review, we discuss known mechanisms and recent scientific advancements regarding osteosarcoma and its patterns of resistance against chemotherapy, radiation, and other newly-introduced therapeutics.

show abstract

Section: Autophagymentioning

confidence: 99%

Section: Autophagymentioning

confidence: 99%

Section: Autophagymentioning

confidence: 99%

See 1 more Smart Citation

Recent Insights into Therapy Resistance in Osteosarcoma

Prudowsky

Yustein

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…So, HIF-2α was mostly described as a major driver in OTS cells with specific metabolic switch [ 40 ]. mTOR was frequently involved in direct links with autophagic processes and was associated with Pi3K/AKT upstream signaling stimulated by different tyrosine kinase receptors [ 62 , 63 , 64 ], combining an OTS cell and tumor microenvironment effect. Nevertheless, it is for instance not so clear how all those biomarkers specifically interact during OTS progression and metastatic propension, as hypoxia is present since the OTS cell initiation.…”

Section: Presence Of Hypoxic Biomarkers In Osteosarcomas Is Relatementioning

confidence: 99%

Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability

Pierrevelcin

Fuchs

Lhermitte

et al. 2020

Cells

View full text Add to dashboard Cite

Osteosarcoma is the most frequent primary bone tumor diagnosed during adolescence and young adulthood. It is associated with the worst outcomes in the case of poor response to chemotherapy and in metastatic disease. While no molecular biomarkers are clearly and currently associated with those worse situations, the study of pathways involved in the high level of tumor necrosis and in the immune/metabolic intra-tumor environment seems to be a way to understand these resistant and progressive osteosarcomas. In this review, we provide an updated overview of the role of hypoxia in osteosarcoma oncogenesis, progression and during treatment. We describe the role of normoxic/hypoxic environment in normal tissues, bones and osteosarcomas to understand their role and to estimate their druggability. We focus particularly on the role of intra-tumor hypoxia in osteosarcoma cell resistance to treatments and its impact in its endogenous immune component. Together, these previously published observations conduct us to present potential perspectives on the use of therapies targeting hypoxia pathways. These therapies could afford new treatment approaches in this bone cancer. Nevertheless, to study the osteosarcoma cell druggability, we now need specific in vitro models closely mimicking the tumor, its intra-tumor hypoxia and the immune microenvironment to more accurately predict treatment efficacy and be complementary to mouse models.

show abstract

“… 2 However, the prognosis is still dissatisfactory because of the high rates of drug resistance, relapse, and metastasis. 3 Thus, more researches are urgently needed to clarify the molecular mechanisms and highlight the potential therapeutic targets of OS.…”

Section: Introductionmentioning

confidence: 99%

<p>LncRNA CASC15 is Upregulated in Osteosarcoma Plasma Exosomes and CASC15 Knockdown Inhibits Osteosarcoma Progression by Regulating miR-338-3p/RAB14 Axis</p>

Zhang

Wang

Ren

et al. 2020

OTT

Self Cite

View full text Add to dashboard Cite

Background: Currently, plenty of studies have demonstrated that lncRNAs can act as crucial roles during the progression of various tumors, including osteosarcoma (OS), and emerging evidences indicated that lncRNAs are abundant and stable in exosomes. The objective of this study is to reveal the dysregulated lncRNAs in OS plasma exosomes and explore their functions in OS. Materials and Methods: Microarray was performed to analyze dysregulated exosomal lncRNAs. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among cancer susceptibility 15 (CASC15), miR-338-3p, and RAB14. Cck-8, colony formation assay, and transwell assay were performed to explore and characterize the effects of CASC15 on OS cells. Animal experiments were used to verify the effects of CASC15 in vivo. Results: Upregulated CASC15 was observed in OS plasma exosomes compared with control, and the same expression was observed in the OS tissues and cell lines. Further assays indicated that CASC15 knockdown could restrain the proliferation, migration, and invasion of OS cells, and inhibit the growth of OS in xenograft models. Furthermore, our results demonstrated CASC15 regulated OS progression via acting as miR-338-3p sponge, and RAB14 was a direct downstream target of miR-338-3p. Rescue experiments verified CASC15 promotes OS cell growth and metastasis by upregulating RAB14 expression. Conclusion: Overall, our findings indicate that CASC15 plays a key role in OS progression by targeting the miR-338-3p/RAB14 axis and can serve as a possible therapeutic target for OS patients.

show abstract

Insight Into the Role of Autophagy in Osteosarcoma and Its Therapeutic Implication

Cited by 47 publications

References 102 publications

Recent Insights into Therapy Resistance in Osteosarcoma

Recent Insights into Therapy Resistance in Osteosarcoma

Focus on Hypoxia-Related Pathways in Pediatric Osteosarcomas and Their Druggability

<p>LncRNA CASC15 is Upregulated in Osteosarcoma Plasma Exosomes and CASC15 Knockdown Inhibits Osteosarcoma Progression by Regulating miR-338-3p/RAB14 Axis</p>

Contact Info

Product

Resources

About