mTOR: An attractive therapeutic target for osteosarcoma?

Ding, Lei; Liu, Cong‑Wei; Qing, Bei; Yang, Tao; Ruiguo, Wang; Yu, Heze; Dou, Bo; Li, Zhihong

doi:10.18632/oncotarget.9305

Cited by 40 publications

(44 citation statements)

References 80 publications

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“…Recent research has reported the aberrant activation of mTOR in OS . Focal adhesion kinase is reported to regulate the activity of the AKT pathway, suggesting a possible mechanistic link in OS .…”

Section: Resultsmentioning

confidence: 99%

“…Recent research has reported the aberrant activation of mTOR in OS. (18) Focal adhesion kinase is reported to regulate the activity of the AKT pathway, suggesting a possible mechanistic link in OS. (19) Therefore, we chose 143B and MG63 cell lines, which were most sensitive to PF562271 treatment, to examine the expression of the AKT/mTOR pathway after PF562271 treatment for 24 h. PF562271 downregulated FAK (Y397), AKT (S473), and mTOR (S2448) phosphorylation at concentrations that impaired cell growth and colony formation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Target therapy in OS is still in its infancy . However, studies have shown that aberrant activation of mTOR has been detected in OS and activation of mTOR is associated with OS cell growth, proliferation, and metastasis . Inhibiting this pathway might be a promising approach for treating OS.…”

Section: Discussionmentioning

confidence: 99%

“…(28,29) However, studies have shown that aberrant activation of mTOR has been detected in OS and activation of mTOR is associated with OS cell growth, proliferation, and metastasis. (18,30) Inhibiting this pathway might be a promising approach for treating OS. In addition, using a combination of inhibitors that target of multiple nodes in a critical cancer pathway was suggested to improve response and prevent the development of resistance.…”

Section: Discussionmentioning

confidence: 99%

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Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

Wen

et al. 2017

Cancer Science

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Focal adhesion kinase (FAK) overexpression is related to invasive and metastatic properties in different kinds of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatments, but its effect in human osteosarcoma has not been well studied. In the present study, we analyzed the antitumor efficacy of PF562271, an FAK inhibitor, against osteosarcoma in vitro and in vivo. Phosphorylated FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed proliferation and colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired the tube formation ability of endothelial cells in vitro. Finally, oral treatment with PF562271 in mice dramatically reduced tumor volume, weight, and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

Wen

et al. 2017

Cancer Science

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“…The aberrant expression of mTor has been shown to be essential for the tumorigenesis of the majority of all cancers [8–11], including OS [12]. Recently, the membrane-associated E3 ubiquitin ligase ZNRF2 has been shown to be involved in the activation and regulation of mTor through protein interaction [13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo-resistance via ZNRF2

Xiao

et al. 2017

Oncotarget

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Osteosarcoma (OS) is a prevalent cancer worldwide. MicroRNAs (miRNAs) play critical roles in the growth, invasion and carcinogenesis of OS, whereas the underlying mechanisms remain ill-defined. Here, we addressed these questions. We detected significantly higher levels of ZNRF2, a ubiquitin ligase of the RING superfamily, and significantly lower levels of miR-100 in the OS specimens, compared to the paired normal bone tissues. The levels of ZNRF2 and miR-100 inversely correlated in the OS specimens. In addition, low miR-100 levels are associated with poor prognosis of the OS patients. Either ZNRF2 overexpression or miR-100 depletion increased in vitro OS cell growth and improved cell survival at the presence of Doxorubicin. Mechanistically, with the help of bioinformatics analysis and luciferase-reporter assay, we found that miR-100 might bind to the 3’-UTR of ZNRF2 mRNA to prevent its protein translation. Thus, our data suggest that re-expression of miR-100 may inhibit OS cell growth and decrease OS cell chemo-resistance.

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Targeted Delivery of PD‐L1‐Derived Phosphorylation‐Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment

Guo

Jing

et al. 2022

Adv Healthcare Materials

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Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle

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mTOR: An attractive therapeutic target for osteosarcoma?

Cited by 40 publications

References 80 publications

Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo-resistance via ZNRF2

Targeted Delivery of PD‐L1‐Derived Phosphorylation‐Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment

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