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Review
. 2024 Feb 4;29(3):721.
doi: 10.3390/molecules29030721.

The Role of the PTEN Tumor Suppressor Gene and Its Anti-Angiogenic Activity in Melanoma and Other Cancers

Jacqueline Maphutha  1 , Danielle Twilley  1 , Namrita Lall  1   2   3
Affiliations
Review

The Role of the PTEN Tumor Suppressor Gene and Its Anti-Angiogenic Activity in Melanoma and Other Cancers

Jacqueline Maphutha et al. Molecules. .

Abstract

Human malignant melanoma and other solid cancers are largely driven by the inactivation of tumor suppressor genes and angiogenesis. Conventional treatments for cancer (surgery, radiation therapy, and chemotherapy) are employed as first-line treatments for solid cancers but are often ineffective as monotherapies due to resistance and toxicity. Thus, targeted therapies, such as bevacizumab, which targets vascular endothelial growth factor, have been approved by the US Food and Drug Administration (FDA) as angiogenesis inhibitors. The downregulation of the tumor suppressor, phosphatase tensin homolog (PTEN), occurs in 30-40% of human malignant melanomas, thereby elucidating the importance of the upregulation of PTEN activity. Phosphatase tensin homolog (PTEN) is modulated at the transcriptional, translational, and post-translational levels and regulates key signaling pathways such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways, which also drive angiogenesis. This review discusses the inhibition of angiogenesis through the upregulation of PTEN and the inhibition of hypoxia-inducible factor 1 alpha (HIF-1-α) in human malignant melanoma, as no targeted therapies have been approved by the FDA for the inhibition of angiogenesis in human malignant melanoma. The emergence of nanocarrier formulations to enhance the pharmacokinetic profile of phytochemicals that upregulate PTEN activity and improve the upregulation of PTEN has also been discussed.

Keywords: angiogenesis; cancer; melanoma; nanocarrier formulations; phosphatase tensin homolog; vascular endothelial growth factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Depiction of the phosphatase tensin homolog (PTEN) gene, comprised of the N-terminal domain, PIP2 binding motif, phosphatase domain, C2 domain, PDZ binding motif, and C-terminal domain.
Figure 2
Figure 2
Depiction of the pro-angiogenic factors that lead to the transition from normal vasculature to abnormal vasculature. Anti-angiogenic factors and anti-angiogenic drugs (Bevacizumab) revert abnormal vasculature to normal vasculature.
See this image and copyright information in PMC

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