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Review
. 2024 Jan 15;25(2):1067.
doi: 10.3390/ijms25021067.

The TGF-β Family in Glioblastoma

Irene Golán-Cancela  1 , Laia Caja  1
Affiliations
Review

The TGF-β Family in Glioblastoma

Irene Golán-Cancela et al. Int J Mol Sci. .

Abstract

Members of the transforming growth factor β (TGF-β) family have been implicated in the biology of several cancers. In this review, we focus on the role of TGFβ and bone morphogenetic protein (BMP) signaling in glioblastoma. Glioblastoma (GBM) is the most common malignant brain tumor in adults; it presents at a median age of 64 years, but can occur at any age, including childhood. Unfortunately, there is no cure, and even patients undergoing current treatments (surgical resection, radiotherapy, and chemotherapy) have a median survival of 15 months. There is a great need to identify new therapeutic targets to improve the treatment of GBM patients. TGF-βs signaling promotes tumorigenesis in glioblastoma, while BMPs suppress tumorigenic potential by inducing tumor cell differentiation. In this review, we discuss the actions of TGF-βs and BMPs on cancer cells as well as in the tumor microenvironment, and their use in potential therapeutic intervention.

Keywords: BMP; TGF-β; glioblastoma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Transforming growth factor β (TGF-β) and bone morphogenetic proteins (BMP) signaling pathway. The canonical signaling pathway for TGF-β and BMP occurs through R-SMAD proteins, SMAD2/3 for TGF-β and SMAD1/5/8 for BMP. In both cases, Co-SMAD4 forms a complex with R-SMADs, and the timeric complex is translocated into the nucleus where it functions as a transcription factor. I-SMAD6/7 act as negative regulators of TGF-β and BMP signaling. The non-canonical signaling pathway works through non-SMAD proteins like ERK-MAP kinase, p38/JNK, RhoA/ROCK, JAK/STAT, or PI3K/AKT/mTOR. Created with BioRender.com.
Figure 2
Figure 2
The roles of TGF-β and BMP in the glioblastoma microenvironment. Tumor-infiltrating immune cells contribute to the immunosuppressive microenvironment through the communication established between them and the tumor cells via TGF-β. TGF-β also supports cell plasticity by helping the differentiation of cancer stem cells (CSCs) to pericytes, and self-renewal of CSCs. On the other hand, BMPs contribute to cell differentiation, from CSCs to differentiated tumor cells. Both TGF-β and BMPs, together with epithelial to mesenchymal transcription factors (EMT-TF), have important roles in the acquisition of migratory characteristics by tumor cells. Created with BioRender.com.
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