Regulation of the tumor suppressor PTEN in triple-negative breast cancer

Chengsen Chai; H Helena Wu; Yasser Abuetabh; Consolato Sergi; Roger Leng

doi:10.1016/j.canlet.2021.12.003

Regulation of the tumor suppressor PTEN in triple-negative breast cancer

Cancer Lett. 2022 Feb 28:527:41-48. doi: 10.1016/j.canlet.2021.12.003. Epub 2021 Dec 10.

Authors

Chengsen Chai¹, H Helena Wu², Yasser Abuetabh², Consolato Sergi³, Roger Leng⁴

Affiliations

¹ 370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Key Laboratory of Clinical Laboratory Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
² 370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
³ Division of Anatomical Pathology, Children's Hospital of Eastern Ontario (CHEO), University of Ottawa, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
⁴ 370 Heritage Medical Research Center, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Electronic address: rleng@ualberta.ca.

PMID: 34902523
DOI: 10.1016/j.canlet.2021.12.003

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BCa) in which estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) are not expressed. Although TNBC cases account for approximately 15% of all BCa cases, TNBC patients' prognosis is poor compared with that of other BCa subtypes. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays an important role in cell proliferation and migration by negatively regulating the PI3K/Akt pathway. PTEN is one of the most commonly inactivated tumor suppressors in BCa. PTEN inactivity is associated with larger tumor sizes, multiple lymph node metastases, and an aggressive triple-negative phenotype. This review primarily focuses on two key points: (1) PTEN and its function. (2) The regulation of tumor suppressor PTEN in TNBC. We provide a summary of genomic alterations of PTEN in BCa. We further discuss the transcriptional regulation of PTEN and how PTEN is regulated by posttranscription and posttranslational modification, as well as by protein interactions. Finally, we discuss the perspectives of the PTEN protein in TNBC.

Keywords: PI3K-AKT pathway; PTEN; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Female
Genomics / methods*
Humans
PTEN Phosphohydrolase / metabolism*
Triple Negative Breast Neoplasms / genetics*

Substances

PTEN Phosphohydrolase
PTEN protein, human

Grants and funding

CIHR/Canada