PTEN, a Tumor Suppressor 1

PTEN controls AKT signaling and serves as a tumor suppressor

PI3K/AKT/mTOR image: PTEN converts PIP3 back to PI4,5P2, thus acting as a negative regulator of the pathway

FOXO=Forkhead box O; GSK3=glycogen synthase kinase 3; mTORC=mammalian target of rapamycin complex; PDK1=phosphoinositide-dependent kinase-1; PI3K=phosphatidylinositol 3-kinase; PI4,5P2=phosphatidylinositol 4,5-bisphosphate; PIP3=phosphatidylinositol 3,4,5-trisphosphate; PTEN=phosphatase and tensin homolog; RTK=receptor tyrosine kinase.

Phosphatase and tensin homolog (PTEN) acts as a negative regulator of the PI3K/AKT pathway through its ability to convert phosphatidylinositol 3,4,5-trisphosphate (PIP3) to phosphatidylinositol 4,5-bisphosphate (PI4,5P2).1,2 Inactivating mutations or loss of heterozygosity in PTEN can lead to the hyperactivation of AKT signaling and increase the risk of cancer development.2

Germline mutations in PTEN have been described in a number of syndromes collectively known as PTEN hamartoma tumor syndrome (PHTS).1 Patients with PHTS have an increased incidence of breast, thyroid, and endometrial cancers, and PTEN is among the most commonly mutated tumor-suppressor genes in sporadic cancer. It has also been implicated in the development of multiple cancer types, including prostate, breast, endometrium, thyroid, central nervous system, lung, pancreas, liver, and adrenal glands. Additionally, it has been involved in cases of melanoma, leukemia, and lymphoma.1 Cancer types with high prevalence of PTEN mutation include uterine, brain, and lung.3

References

  1. Hollander MC, Blumenthal GM, Dennis PA. Nat Rev Cancer. 2011;11:289-301. PMID: 21430697
  2. Manning BD, Toker A. Cell. 2017;169:381-405. PMID: 28431241
  3. National Cancer Institute. GDC data portal. https://portal.gdc.cancer.gov/. Data released August 23, 2018. Accessed September 12, 2018.