Targeting ROR1 inhibits the self‐renewal and invasive ability of glioblastoma stem cells

Jung, Eun Hwa; Lee, Han Na; Han, Gi Yeon; Kim, Min Jung; Kim, Chan Wha

doi:10.1002/cbf.3172

Cited by 20 publications

(20 citation statements)

References 34 publications

(75 reference statements)

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“…The invasion capabilities of GSCs also contributes to the initiation of cancer metastasis (31). As such, the anti-invasive potential of CK on GSCs from U87MG and U373MG cells was evaluated.…”

Section: Resultsmentioning

confidence: 99%

The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells

Lee

Kwon

Jang

et al. 2017

International Journal of Oncology

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Glioblastoma (GBM) is the most aggressive and malignant form of primary brain cancer. Despite recent advances in cancer treatment, it remains a substantially incurable disease. Accordingly, more effective GBM therapeutic options are urgently required. In the present study, we investigated the anticancer effect of a ginsenoside metabolite, compound K (CK), against GBM cells. CK significantly inhibited not only growth, but also metastatic ability of U87MG and U373MG cells. CK arrested cell cycle progression at the G0/G1 phase with a decrease in the expression levels of cyclin D1 and cyclin D3 in both cell types. CK also induced apoptosis in GBM cells through nuclear condensation, an increase in ROS generation, mitochondrial membrane potential depolarization, and activation of caspase-3, caspase-9 and poly(ADP-ribose) polymerase (PARP). Furthermore, CK inhibited phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, contributing to the antiproliferative and apoptotic effects. Moreover, CK suppressed the self-renewal capacity as well as the invasiveness of U87MG and U373MG GBM stem-like cells (GSCs) by inducing a reduction in the expression of GSC markers, such as CD133, Nanog, Oct4 and Sox2. Taken together, our findings suggest that CK may potentially be useful for GBM treatment.

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Section: Resultsmentioning

confidence: 99%

The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells

Lee

Kwon

Jang

et al. 2017

International Journal of Oncology

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“…Similarly, the data reported on by Liu et al suggested that silencing ROR1 critically associated with the inhibition of cell growth and the induction of cell apoptosis in lung cancer via PI3K/AKT/mTOR signaling pathway . In glioblastoma, Jung et al illustrated that knockdown of ROR1 severely inhibited tumor stemness, sphere formation, migratory action and invasive ability . In addition, a monoclonal anti‐ROR1 Fab antibody could inhibit tumor cell proliferation and migration, while inducing tumor cell apoptosis .…”

Section: Discussionmentioning

confidence: 99%

ROR1 associates unfavorable prognosis and promotes lymphoma growth in DLBCL by affecting PI3K/Akt/mTOR signaling pathway

Yuan

Wang

et al. 2019

BioFactors

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The receptor-tyrosine-kinase (RTK)-like orphan receptor 1 (ROR1) is a transmembrane glycoprotein regarded as a tumor-associated antigen. ROR1 plays an important role in cancer development, but the detailed function of ROR1 in diffuse large B-cell lymphoma (DLBCL) remains unclear. In this study, we first detected ROR1 expression and evaluated the relationship between ROR1 expression and the clinicopathological characteristics of DLBCL patients. Next we employed shRNA-mediated knockdown of ROR1 in DLBCL cell line to explore the characteristics of ROR1 in DLBCL development both in vitro and in vivo. The results showed a significantly higher level of ROR1 in DLBCL tissues than in lymphatic hyperplasia tissues. High ROR1 expression was correlated with unfavorable prognosis in DLBCL patients. Furthermore, ROR1 knockdown inhibited the growth and BioFactors 416Research Communication induced the apoptosis in DLBCL cells and xenografts. In addition, shROR1 inhibited activation of the PI3K/Akt/mTOR signaling pathway, both in vitro and in vivo. Taken together, our results suggest that ROR1 is a novel prognostic marker for DLBCL survival and ROR1 significantly promotes DLBCL tumorigenesis by regulating the PI3K/Akt/mTOR signaling pathway. Targeting ROR1 may provide a promising strategy for DLBCL treatment.

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“…Moreover, it was shown that down-regulation of Ror1 suppressed the expression of EMTrelated genes and the migratory and invasive abilities of the tumour. The results of this study indicated that targeting Ror1 could induce differentiation of cancer stem cells (CSCs) and inhibit metastasis in glioblastoma 15 . In a recent report, it was also shown that siRNAs targeting Ror1 in CLL induced apoptosis and a small molecule inhibitor, Ror1 tyrosine kinase inhibitor dephosphorylated Ror1, down-regulating the activated PI3K/AKT/mTOR signaling pathway and inducing specific apoptosis of CLL cells 66 .…”

Section: Discussionmentioning

confidence: 87%

“…Although, Ror1 does not express itself virtually in all normal adult tissues, it re-expresses in many tissues during some B-cell malignancies, and various cancer cell lines 6, 8, 15, 16 . Ror1 was significantly more expressed in various tumours such as acute lymphocytic leukemia, renal carcinoma, breast cancer, lung cancer, adenocarcinoma and melanoma 16–21 .…”

Section: Introductionmentioning

confidence: 99%

In-Silico Drug discovery approach targeting receptor tyrosine kinase-like orphan receptor 1 for cancer treatment

Nath

Singh

2017

Sci Rep

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Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils. The prediction of the active site revealed its cage-like function that opens for ligand entry and then closes for interacting with the ligands. Optimized ligands from the database were virtually screened to obtain the most efficient and potent ones. The screened ligands were evaluated for their therapeutic usefulness. Furthermore, the ligands that passed the test were docked to the target protein resulting in a few ligands with high score, which were analyzed further. The highest scoring ligand, Beta-1, 2,3,4,6-Penta-O-Galloyl-D-Glucopyranose was reported to be a naturally occurring tannin. This in silico approach indicates the potential of this molecule for advancing a further step in cancer treatment.

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Targeting ROR1 inhibits the self‐renewal and invasive ability of glioblastoma stem cells

Cited by 20 publications

References 34 publications

The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells

The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells

ROR1 associates unfavorable prognosis and promotes lymphoma growth in DLBCL by affecting PI3K/Akt/mTOR signaling pathway

In-Silico Drug discovery approach targeting receptor tyrosine kinase-like orphan receptor 1 for cancer treatment

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