SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/β-catenin signaling through stabilization of the WNT–receptor complex

Sj, Zhao; Yq, Jiang; Nw, Xu; Q, Li; Zhang, Q; Sy, Wang; Li, Jian; Wang, YH; Yl, Zhang; Jiang, Song; Yj, Wang; Yj, Huang; Xx, Zhang; Ga, Tian; Zhang, CC; Yy, Lv; Dai, Mingjun; F, Liu; Zhang, R; Zhou, Dong; Zg, Zhang

doi:10.1038/onc.2017.403

Cited by 64 publications

(47 citation statements)

References 49 publications

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“…The functional role of the Wnt signaling pathway in OS is not completely understood ( 23 ). A number of studies support the idea that the Wnt signaling pathway serves an anti-tumorigenic effect in OS ( 24 – 26 ), whereas other studies suggest that aberrant activation of the canonical Wnt signaling pathway serves an important role in OS initiation, maintenance and resistance to chemotherapy ( 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

Chen

et al. 2020

Oncol Lett

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Osteosarcoma (OS) is a common bone tumor with high mortality worldwide. The long-term survival rate of patients with metastatic or recurrent disease is <20%. The present study explored the biological role of microRNA (miRNA/miR)-1236-3p in OS. miRNA and mRNA expression levels were measured via reverse transcription-quantitative PCR. Fluorescence in situ hybridization was performed to determine miR-1236-3p expression levels in clinical specimens. Protein expression was measured via western blotting. Immunohistochemical analysis was used to detect Wnt target gene expression in tumor tissues. The interaction between the Wnt3a 3′untranslated region and miR-1236-3p was assessed via dual-luciferase reporter assays. Cell cycle, Transwell, Cell Counting Kit-8 and wound healing assays were conducted to evaluate the function of the miR-1236-3p/Wnt3a axis. Human OS (HOS) cells stably transfected with vector or miR-1236-3p sponge were injected subcutaneously into nude mice to assess the role of miR-1236-3p in vivo . miR-1236-3p expression was downregulated in OS tissues compared with chondroma tissues, and miR-1236-3p overexpression inhibited OS cell migration and proliferation compared with the negative control group. Furthermore, in vivo xenograft assays displayed enhanced tumour growth rates in the miR-1236-3p sponge group compared with the vector control group. In the present study, the results indicated that miR-1236-3p inhibited OS progression and Wnt3a was identified as a target of miR-1236-3p.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

Chen

et al. 2020

Oncol Lett

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“…Secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) is a member of the SPARC family, which is associated with various biological behaviors including osteoblast differentiation and development of cancers. Previous studies have suggested SPARCL1 as a potential tumor suppressor (5)(6)(7). Low SPARCL1 expression is associated with the development and progression of cervical cancer (8).…”

Section: Introductionmentioning

confidence: 98%

“…Low SPARCL1 expression is associated with the development and progression of cervical cancer (8). Zhao et al (5) detected that SPARCL1 was significantly down-regulated in human osteosarcoma cell lines and clinical tissue samples. Interestingly, a recent study revealed that SPARCL1 was strongly down-regulated by 6.4-fold in 594 ovarian cancer cases compared with eight normal ovaries and was suspected to contribute to tumor invasiveness (9).…”

Section: Introductionmentioning

confidence: 99%

SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells via the MEK/ERK signaling

2018

Exp Ther Med

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Ovarian cancer is the most lethal gynecological malignancy worldwide and is one of the five leading causes of cancer-associated mortality in women. There is an urgent requirement to obtain a greater understanding of the molecular mechanism underlying ovarian cancer progression in order to identify novel drug targets and biomarkers. Secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) has been suggested as a candidate tumor suppressor in various types of human cancers. However, the potential role of SPARCL1 for ovarian cancer has not yet been clearly established. In the present study, lower protein expression levels of SPARCL1 were detected in ovarian cancer tissues when compared with adjacent normal tissues. Overexpression of SPARCL1 significantly suppressed the proliferation and migration of cells from the ovarian cancer cell line SKOV-3, whereas knockdown of SPARCL1 significantly increased cell growth and migration. Furthermore, the results revealed that SPARCL1 overexpression significantly suppressed the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. Collectively, these results indicated that SPARCL1 may suppress the proliferation and migration of ovarian cancer cells by downregulating signaling via the MEK/ERK pathway.

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“…Another patient displayed a RICTOR-CCDC152 fusion (Figure 5C and D). A fusion transcript RORA-LHFP composed of RORA exon 1 fused to LHFP exon 3 is shown in Figure 5E and F. The three fusion genes are speculated to be involved in tumor growth, as their partners have important roles in malignant diseases (24)(25)(26).…”

Section: Pseudogenes Are Involved In Formation Of Gene Fusionmentioning

confidence: 99%

Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

Zheng

Zhang

Cai

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm characterized by chromosomal instability. The aim of this study was to identify fusion events involved in UPS. Materials and Methods: Transcriptome sequencing was performed to search for new fusion genes in 19 UPS samples, including two paired recurrent (R) and re-recurrent (RR) samples. Results: A total of 66 fusion genes were detected. Among them, 10 novel fusion genes were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing. Retinoblastoma (RB1) fusions (2 cases) were the most recurrent fusion genes. The gene fusions RB1-RNASEH2B, RB1-FGF14-AS1, and E2F6-FKBP4 were correlated with the Rb/E2F pathway. Pseudogenes were involved in the formation of the gene fusions CIC-DUX4L8 and EIF2AK4-ANXA2P2. Importantly, targetable gene fusions (PDGFRA-MACROD2 and NCOR1-MAP2K1) were detected in UPS. Conclusion: Screening for the presence of fusion transcripts will provide vital clues to the understanding of genetic alterations and the finding of new targeted therapies for UPS.

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SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/β-catenin signaling through stabilization of the WNT–receptor complex

Cited by 64 publications

References 49 publications

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells via the MEK/ERK signaling

Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

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