Phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as therapeutic targets in breast cancer

Abstract

Breast cancer is the most commonly diagnosed cancer among women in Turkey and worldwide. It is considered a heterogeneous disease and has different subtypes. Moreover, breast cancer has different molecular characteristics, behaviors, and responses to treatment. Advances in the understanding of the molecular mechanisms implicated in breast cancer progression have led to the identification of many potential therapeutic gene targets, such as Breast Cancer 1/2, phosphatidylinositol 3-kinase catalytic subunit alpha, and tumor protein 53. The aim of this review is to summarize the roles of phosphatidylinositol 3-kinase regulatory subunit 1 (alpha) (alias p85α) and phosphatase and tensin homolog in breast cancer progression and the molecular mechanisms involved. Phosphatase and tensin homolog is a tumor suppressor gene and protein. Phosphatase and tensin homolog antagonizes the phosphatidylinositol 3-kinase/ AKT signaling pathway that plays a key role in cell growth, differentiation, and survival. Loss of phosphatase and tensin homolog expression, detected in about 20%-30% of cases, is known to be one of the most common tumor changes leading to phosphatidylinositol 3-kinase pathway activation in breast cancer. Instead, the regulatory subunit p85α is a significant component of the phosphatidylinositol 3-kinase pathway, and it has been proposed that a reduction in p85α protein would lead to decreased negative regulation of phosphatidylinositol 3-kinase and hyperactivation of the phosphatidylinositol 3-kinase pathway. Phosphatidylinositol 3-kinase regulatory subunit 1 protein has also been reported to be a positive regulator of phosphatase and tensin homolog via the stabilization of this protein. A functional genetic alteration of phosphatidylinositol 3-kinase regulatory subunit 1 that results in reduced p85α protein expression and increased insulin receptor substrate 1 binding would lead to enhanced phosphatidylinositol 3-kinase signaling and hence cancer development. Phosphatidylinositol 3-kinase regulatory subunit 1 underexpression was observed in 61.8% of breast cancer samples. Therefore, expression/alternations of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog genes have crucial roles for breast cancer progression. This review will summarize the biological roles of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog in breast cancer, with an emphasis on recent findings and the potential of phosphatidylinositol 3-kinase regulatory subunit 1 and phosphatase and tensin homolog as a therapeutic target for breast cancer therapy. KeywordsPhosphatidylinositol 3-kinase regulatory subunit 1, phosphatase and tensin homolog, phosphatidylinositol 3-kinase, breast cancer, therapy, phosphatidylinositol 3-kinase catalytic subunit alpha Date

Role of LGMN in tumor development and its progression and connection with the tumor microenvironment

“…LGMN, Integrin Co-activation Epithelial ovarian cancer α5β1/AEP complex affects epithelial ovarian cancer proliferation and migration Quail and Joyce (2013) Frontiers in Molecular Biosciences frontiersin.org Dirican and Akkiprik, 2017;Xu et al, 2021). Inhibiting the expression of LGMN in prostate cells 22RV1 reduced PI3K but had no effect on the Mammalian target of rapamycin (mTOR) protein (Zhu et al, 2016).…”

“…This increases the capacity of breast cancer cells to invade and metastasize. Epithelial-mesenchymal transitions (EMT) also encourage the invasion and metastasis of breast cancer ( Rafael et al, 2015 ; Thapa et al, 2015 ; Dirican and Akkiprik, 2017 ; Xu et al, 2021 ). Inhibiting the expression of LGMN in prostate cells 22RV1 reduced PI3K but had no effect on the Mammalian target of rapamycin (mTOR) protein ( Zhu et al, 2016 ).…”

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

“…PTEN is a well-characterized tumor suppressor gene, which antagonizes the phosphoinositol-3-kinase/protein kinase B (PKB or Akt) signaling pathway [ 12 ]. The PTEN gene acts as a tumor suppressor gene in multiple cancers, including breast cancer [ 13 , 14 ], nasopharyngeal carcinoma [ 15 ], renal cell carcinoma [ 16 ], non-small-cell lung cancer [ 17 ], hepatocellular carcinoma [ 18 ], human NK/T-cell lymphoma [ 19 ], and osteosarcoma [ 20 ]. The loss of function of PTEN in tumor cells results in the accumulation of critical cell messengers, which increases Akt phosphorylation and activity and leads to decreased apoptosis and/or increased mitogenic signaling [ 21 , 22 ].…”

PTEN allelic loss is an important mechanism in the late stage of development of oral leucoplakia into oral squamous cell carcinoma

“…Akt/protein kinase B is a major downstream target of growth factor receptor tyrosine kinase that signals via phosphatidylinositol‐3 kinase (PI3K), and is activated frequently in different human malignancies . Phospho‐Akt (p‐Akt) controls a variety of critical cellular pathways during the carcinogenic process, including those leading to apoptosis inhibition and increased cell proliferation, as well as enhanced tumour cell invasion, angiogenesis and cell metabolism, through glucose metabolism .…”