Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer

Hamilton, Nalo; Austin, David; Márquez-Garbán, Diana C.; Sanchez, Rudy; Chau, Brittney; Foos, Kay; Wu, Yanyuan; Vadgama, Jaydutt V.; Pietras, Richard J.

doi:10.3390/ijms18112305

Cited by 18 publications

(12 citation statements)

References 68 publications

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“…We have also shown that in TNBC cell lines that activation of ERβ results in increased secretion of IGF2 which can bind to IR/IGF1R, and activate growth promoting capabilities. Recent studies have shown that targeting the IGF1R pathway could be a therapeutic target [ 65 , 66 ]. These results and the previous data suggest that endocrine therapy may be beneficial for improving TNBC outcomes.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

et al. 2018

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Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy.Tissue microarrays (TMAs) from over 250 TNBC patients' were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation.TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

et al. 2018

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“…By interaction with specific tyrosine-kinase receptors, insulin-like growth factor-1 receptor (IGF1R) and insulin receptor isoform A (IR-A), IGF2 stimulates downstream actions via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3kinase (PI3K) AKT/protein kinase B (PKB) pathways to stimulate tumor proliferation 9 . A recent study highlights the significant anti-proliferative activities of IGF1R and IR antagonists in TNBC cells in vitro 10 . BMS-754807, an established IGF1R/IR inhibitor, and NVP-AEW541, an IGF1R inhibitor, exhibit anti-proliferative effects on IGF2-expressing TNBC cells, an action dependent in part on AKT activity.…”

Section: Discussionmentioning

confidence: 99%

Dual Therapy with Insulin-Like Growth Factor-I Receptor/Insulin Receptor (IGF1R/IR) and Androgen Receptor (AR) Antagonists Inhibits Triple-Negative Breast Cancer Cell Migration In Vitro

Hamilton¹,

Márquez-Garbán²,

Rogers³

et al. 2019

BIOMEDJ

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“…It promotes the growth of triple-negative breast cancer cells through autocrine and/or paracrine mechanisms. The mechanism may be related to androgen receptor (AR) and estrogen receptor (ER b) (144,145). Therefore, two-way targeted therapy for the IGF-II, AR and ER b signaling pathways is expected to be a potential target for TNBC treatment.…”

Section: Insulin-like Growth Factor-ii (Igf-ii) and Tumorsmentioning

confidence: 99%

Targeting Adipokines in Obesity-Related Tumors

Chen

2021

Front. Oncol.

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Obesity, a global epidemic, is an independent risk factor for the occurrence and development of a variety of tumorigenesis, such as breast cancer, pancreatic cancer, ovarian cancer and colorectal cancer. Adipocytes are important endocrine cells in the tumor microenvironment of obesity-related tumors, which can secrete a variety of adipokines (such as leptin, adiponectin, estrogen, resistin, MIF and MCP-1, etc.), among which leptin, adiponectin and estrogen are the most in-depth and valuable ones. These adipokines are closely related to tumorigenesis and the progression of tumors. In recent years, more and more studies have shown that under chronic inflammatory conditions such as obesity, adipocytes secrete more adipokines to promote the tumorigenesis and development of tumors. However, it is worth noting that although adiponectin is also secreted by adipocytes, it has an anti-tumor effect, and can cross-talk with other adipokines (such as leptin and estrogen) and insulin to play an anti-tumor effect together. In addition, obesity is the main cause of insulin resistance, which can lead to the increase of the expression levels of insulin and insulin-like growth factor (IGF). As important regulators of blood glucose and lipid metabolism, insulin and IGF also play an important role in the progress of obesity related tumors. In view of the important role of adipokines secreted by adipocytes and insulin/IGF in tumors, this article not only elaborates leptin, adiponectin and estrogen secreted by adipocytes and their mechanism of action in the development of obesity- related tumors, but also introduces the relationship between insulin/IGF, a regulator of lipid metabolism, and obesity related tumors. At the same time, it briefly describes the cancer-promoting mechanism of resistin, MIF and MCP-1 in obesity-related tumors, and finally summarizes the specific treatment opinions and measures for various adipokines and insulin/insulin-like growth factors in recent years.

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Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer

Cited by 18 publications

References 68 publications

Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

Dual Therapy with Insulin-Like Growth Factor-I Receptor/Insulin Receptor (IGF1R/IR) and Androgen Receptor (AR) Antagonists Inhibits Triple-Negative Breast Cancer Cell Migration In Vitro

Targeting Adipokines in Obesity-Related Tumors

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