TGF-β is associated with poor prognosis and promotes osteosarcoma progression via PI3K/Akt pathway activation.

Abstract

Transforming growth factor beta (TGF-β) is a multifunctional cytokine with important functions in cell proliferation and differentiation. TGF-β is highly expressed in several types of cancers and promotes tumor invasion and metastasis. However, the role of TGF-β in osteosarcoma progression is poorly understood. In the present study, we found that TGF-β is highly expressed in osteosarcoma cells and tissues, and is associated with high Ennecking stage (P = 0.033), metastasis, and recurrence. TGF-β-knockdown osteosarcoma cell lines were established using siRNA (si-TGF-β). Cells transfected with si-TGF-β exhibited significantly reduced proliferation, migration/invasion, and colony formation abilities, and increased levels of cell apoptosis. In addition, si-TGF-β treatment reduced spheroid size, the ratio of CD133-positive cells, and expression of SOX-2, Nanog, and Oct-3/4 in osteosarcoma cells. Mechanistically, PI3K/mTOR phosphorylation is inhibited by TGF-β knockdown. Pretreatment with 25 µM LY294002, a PI3K-specific inhibitor, further enhanced the si-TGF-β-induced suppression of osteosarcoma progression. Taken together, these results reveal a novel role for TGF-β in osteosarcoma progression and modulation of stemness-related traits and indicate that TGF-β may be of value as a therapeutic target for the treatment of osteosarcoma.

• Authors: Kun Ma, Chuan Zhang, Wuyin Li
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 19 Issue 18 Pg. 2327-2339 (09 2020) ISSN: 1551-4005 [Electronic] United States
• PMID: 32804027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Transforming Growth Factor beta
• MTOR protein, human
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adolescent
• Adult
• Animals
• Apoptosis
• Bone Neoplasms (enzymology, genetics, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Child
• Disease Progression
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Neoplastic Stem Cells (enzymology, pathology)
• Osteosarcoma (enzymology, genetics, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (metabolism)
• Transforming Growth Factor beta (genetics, metabolism)
• Young Adult