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COPS3 inhibition promotes cell proliferation blockage and anoikis via regulating PFKFB3 in osteosarcoma cancer cells

Fan Zhang1, Qianqian Li2, Yaqin Zhang2

  • 1Department of Bone and Soft Tissue Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.

European Journal of Pharmacology
|May 18, 2023
PubMed

Insights

COPS3 protein promotes cancer progression and metastasis by regulating anoikis, a form of apoptosis. This study reveals COPS3 modulates anoikis via PFKFB3 in osteosarcoma cells, impacting cancer treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • COPS3 is a key component of the COP9 signalosome complex, implicated in various physiological processes and linked to multiple cancers.
  • COPS3 promotes cancer cell proliferation, progression, and metastasis, but its role in anoikis and metastasis regulation is unstudied.

Purpose of the Study:

  • To investigate the role of COPS3 in regulating anoikis, a specific form of apoptosis, and its function as a modulator of cell metastasis in cancer.
  • To explore the relationship between COPS3, anoikis, and the efficacy of oxaliplatin (Oxa) treatment in osteosarcoma (OS).

Main Methods:

  • Bioinformatics analysis to assess COPS3 expression in metastatic versus non-metastatic cancer groups and its association with pathways like ECM receptor interaction.
  • In vitro experiments involving COPS3 overexpression and knockdown in osteosarcoma cells, with and without oxaliplatin treatment, to evaluate effects on proliferation, viability, migration, invasion, apoptosis, and anoikis.
  • Investigation of the interaction between COPS3 and PFKFB3 (a glycolysis modulator) and its impact on anoikis and oxaliplatin-induced cell death.

Main Results:

  • COPS3 is highly expressed in several cancers, particularly osteosarcoma, where its overexpression enhances proliferation, viability, and migration/invasion.
  • Knockdown of COPS3 increases oxaliplatin cytotoxicity and influences oxaliplatin-enhanced anoikis.
  • COPS3 interacts with PFKFB3 and functions upstream of it to modulate anoikis in osteosarcoma cells.

Conclusions:

  • COPS3 plays a significant role in regulating anoikis and cell metastasis in osteosarcoma.
  • COPS3 modulates anoikis through the PFKFB3 pathway, influencing cancer cell survival and response to oxaliplatin treatment.
  • Targeting COPS3 or its downstream effectors may offer novel therapeutic strategies for osteosarcoma and other cancers.
Keywords:
AnoikisCOPS3OsteosarcomaOxaliplatinPFKFB3

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