ArticlePloS one2014
CCN2 enhances resistance to cisplatin-mediating cell apoptosis in human osteosarcoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Downregulated of CTGF reveals mechanism, remodels immune microenvironment, modulates drug sensitivity in bladder cancer.Future science OA · 2025Article
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Altered tumor signature and T-cell profile after chemotherapy reveal new therapeutic opportunities in high-grade serous ovarian carcinoma.Cancer science · 2024Article
- CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.Journal of cell communication and signaling · 2021Review
- Encapsulation of Nedaplatin in Novel PEGylated Liposomes Increases Its Cytotoxicity and Genotoxicity against A549 and U2OS Human Cancer Cells.Pharmaceutics · 2020Article
- MicroRNA-584 Impairs Cellular Proliferation and Sensitizes Osteosarcoma Cells to Cisplatin and Taxanes by Targeting CCN2.Cancer management and research · 2020Article
- Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma.Oncology reports · 2019Article
- MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9.Bioscience reports · 2019Article
- Artocarpin induces cell apoptosis in human osteosarcoma cells through endoplasmic reticulum stress and reactive oxygen species.Journal of cellular physiology · 2019Article
- ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer.International journal of molecular sciences · 2019Review
- Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2.Journal of developmental biology · 2018Review
- Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway.Experimental and therapeutic medicine · 2018Article
- PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.Oncotarget · 2017Article
- Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway.Molecular medicine reports · 2017Article
- Targeting of CCN2 suppresses tumor progression and improves chemo-sensitivity in urothelial bladder cancer.Oncotarget · 2017Article
- Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics.Oncotarget · 2017Article
- Role of CTGF in Sensitivity to Hyperthermia in Ovarian and Uterine Cancers.Cell reports · 2016Article
- CCN family of proteins: critical modulators of the tumor cell microenvironment.Journal of cell communication and signaling · 2016Article
- A potential role for CCN2/CTGF in aggressive colorectal cancer.Journal of cell communication and signaling · 2016Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most common form of malignant bone tumor and is an aggressive malignant neoplasm exhibiting osteoblastic differentiation. Cisplatin is one of the most efficacious antitumor drugs for osteosarcoma patients. However, treatment failures are common due to the development of chemoresistance. CCN2 (also known as CTGF), is a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CCN2 in cisplatin-mediated chemotherapy is still unknown. Here, we found that CCN2 was upregulated in human osteosarcoma cells after treatment with cisplatin. Moreover, overexpression of CCN2 increased the resistance to cisplatin-mediated cell apoptosis. In contrast, reduction of CCN2 by CCN2 shRNA promoted the chemotherapeutic effect of cisplatin. We also found that CCN2 provided resistance to cisplatin-induced apoptosis through upregulation of Bcl-xL and survivin. Knockdown of Bcl-xL or survivin removed the CCN2-mediated resistance to apoptosis induced by cisplatin. On the other hand, CCN2 also promoted FAK, MEK, and ERK survival signaling pathways to enhance tumor survival during cisplatin treatment. In a mouse xenograft model, overexpression of CCN2 promoted resistance to cisplatin. However, knockdown of CCN2 increased the therapeutic effect of cisplatin. Therefore, our data suggest that CCN2 might be a critical oncogene of human osteosarcoma for cisplatin-resistance and supported osteosarcoma cell growth in vivo and in vitro.
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