Targeting breast cancer initiating cells: Advances in breast cancer research and therapy

McCubrey, James A.; Davis, Nicole M.; Abrams, Stephen L.; Montalto, Giuseppe; Cervello, Melchiorre; Libra, Massimo; Nicoletti, Ferdinando; D’Assoro, Antonino B.; Cocco, Lucio; Martelli, Alberto M.; Steelman, Linda S.

doi:10.1016/j.jbior.2014.05.003

Cited by 35 publications

(18 citation statements)

References 187 publications

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“…The PI3K/Akt/mTOR signaling pathway is frequently activated in breast cancer (31,32). Activation of this pathway has been associated with resistance to endocrine therapy in patients with ER-positive breast cancer (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of BAG‑1 in T47D cells promotes resistance to tamoxifen via activation of the PI3K/Akt/mTOR signaling pathway

Cui

et al. 2019

Oncol Rep

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Section: Discussionmentioning

confidence: 99%

Downregulation of BAG‑1 in T47D cells promotes resistance to tamoxifen via activation of the PI3K/Akt/mTOR signaling pathway

Cui

et al. 2019

Oncol Rep

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“…In breast cancer, γ-synuclein is overexpressed in later-stage (Stage III and IV) cancer tissues, but not in healthy or early-stage (Stage I and II) cancer tissue [8]. Even though different types of breast cancers are classified by different markers [9], the presence of γ-synuclein been established as a biomarker for later stages of cancer and has been considered to be a prognosis of poor outcome [10]. …”

Section: Introductionmentioning

confidence: 99%

The breast cancer susceptibility gene product (γ-synuclein) alters cell behavior through it interaction with phospholipase Cβ

Yerramilli

Scarlata

2016

Cellular Signalling

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The breast cancer susceptibility gene protein, also known as γ-synuclein, is highly expressed in human breast cancer in a stage-specific manner, with highest expression in late stage cancer. In model systems, γ-synuclein binds phospholipase Cβ2 which is regulated by Gαq to generate intracellular Ca2+ signals. PLCβ2, which is also absent in normal tissue but highly expressed in breast cancer, is additionally regulated by Rac to promote migration pathways. We have found that γ-synuclein binds to the same region of PLCβ2 as Gαq. Using cells that mimic stage 4 breast cancer (MDA MB 231), we show that down-regulation of γ-synuclein reduces the protein level of PLCβ but increases the transcript level over 40 fold. γ-Synuclein down-regulation also promotes the interaction between Gαq and PLCβ resulting in a stronger Ca2+ response to Gαq agonists. The ability of γ-synuclein to interfere with Gαq-PLCβ interactions allows more PLCβ to colocalize with Rac impacting Rac-mediated pathways that may give rise to cancerous phenotypes.

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“…The PI3K/PTEN/AKT/mTORC pathway is frequently dysregulated in many different cancer types including: breast , pancreatic , prostate , brain , leukaemia and others . This pathway is regulated at many steps by tumour suppressor and oncogenes .…”

Section: Introductionmentioning

confidence: 99%

The therapeutic potential of mTOR inhibitors in breast cancer

Steelman

Martelli

Cocco

et al. 2016

Brit J Clinical Pharma

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103

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Rapamycin and modified rapamycins (rapalogs) have been used to prevent allograft rejection after organ transplant for over 15 years. The mechanistic target of rapamycin (mTOR) has been determined to be a key component of the mTORC1 complex which consists of the serine/threonine kinase TOR and at least five other proteins which are involved in regulating its activity. Some of the best characterized substrates of mTORC1 are proteins which are key kinases involved in the regulation of cell growth (e.g., p70S6K) and protein translation (e.g., 4E-BP1). These proteins may in some cases serve as indicators to sensitivity to rapamycinrelated therapies. Dysregulation of mTORC1 activity frequently occurs due to mutations at, or amplifications of, upstream growth factor receptors (e.g., human epidermal growth factor receptor-2, HER2) as well as kinases (e.g., PI3K) and phosphatases (e.g., PTEN) critical in the regulation of cell growth. More recently, it has been shown that certain rapalogs may enhance the effectiveness of hormonal-based therapies for breast cancer patients who have become resistant to endocrine therapy. The combined treatment of certain rapalogs (e.g., everolimus) and aromatase inhibitors (e.g., exemestane) has been approved by the United States Food and Drug Administration (US FDA) and other drug regulatory agencies to treat estrogen receptor positive (ER+) breast cancer patients who have become resistant to hormonal-based therapies and have progressed. This review will summarize recent basic and clinical research in the area and evaluate potential novel therapeutic approaches.

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Targeting breast cancer initiating cells: Advances in breast cancer research and therapy

Cited by 35 publications

References 187 publications

Downregulation of BAG‑1 in T47D cells promotes resistance to tamoxifen via activation of the PI3K/Akt/mTOR signaling pathway

Downregulation of BAG‑1 in T47D cells promotes resistance to tamoxifen via activation of the PI3K/Akt/mTOR signaling pathway

The breast cancer susceptibility gene product (γ-synuclein) alters cell behavior through it interaction with phospholipase Cβ

The therapeutic potential of mTOR inhibitors in breast cancer

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