Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression

Andò, Sebastiano; Naimo, Giuseppina Daniela; Gelsomino, Luca; Catalano, Stefania; Mauro, Loredana

doi:10.1111/obr.13004

Cited by 17 publications

(24 citation statements)

References 175 publications

(265 reference statements)

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“…Adiponectin activates the cytokine signaling responsible for the inactivation of leptin-induced AKT and STAT3 activation as well as Wnt signaling [109,110]. It is suggested that low levels of adiponectin are associated with high grade tumors, which might be due to an interference in its signaling via AMPK, which has an antiproliferative effect [111]. Studies also suggest that considering leptin or adiponectin concentration individually in plasma is not correct, the true measurement is the ratio of the two, as different concentrations of each can be found in BC cell lines [112][113][114][115].…”

Section: Adiponectinmentioning

confidence: 99%

The Importance of Breast Adipose Tissue in Breast Cancer

Kothari

Diorio

Durocher

2020

IJMS

112

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Adipose tissue is a complex endocrine organ, with a role in obesity and cancer. Adipose tissue is generally linked to excessive body fat, and it is well known that the female breast is rich in adipose tissue. Hence, one can wonder: what is the role of adipose tissue in the breast and why is it required? Adipose tissue as an organ consists of adipocytes, an extracellular matrix (ECM) and immune cells, with a significant role in the dynamics of breast changes throughout the life span of a female breast from puberty, pregnancy, lactation and involution. In this review, we will discuss the importance of breast adipose tissue in breast development and its involvement in breast changes happening during pregnancy, lactation and involution. We will focus on understanding the biology of breast adipose tissue, with an overview on its involvement in the various steps of breast cancer development and progression. The interaction between the breast adipose tissue surrounding cancer cells and vice-versa modifies the tumor microenvironment in favor of cancer. Understanding this mutual interaction and the role of breast adipose tissue in the tumor microenvironment could potentially raise the possibility of overcoming breast adipose tissue mediated resistance to therapies and finding novel candidates to target breast cancer.

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Section: Adiponectinmentioning

confidence: 99%

The Importance of Breast Adipose Tissue in Breast Cancer

Kothari

Diorio

Durocher

2020

IJMS

112

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“…In ERα-positive breast cancer cells, LKB1 binds to ERα and in doing so makes its cytosolic pool not adequate to activate AMPK signaling, thus maintaining mTOR signaling and sustaining cell growth ( Ando et al, 2020 ). To investigate the biological effect of ER-α on tumorigenesis in ER-α-positive EC, mRNA and protein levels of genes in the LKB1/AMPK/mTOR pathway were determined.…”

Section: Resultsmentioning

confidence: 99%

Artesunate Suppresses the Proliferation and Development of Estrogen Receptor-α-Positive Endometrial Cancer in HAND2-Dependent Pathway

Yin

Liu

Qin

et al. 2021

Front. Cell Dev. Biol.

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Endometrial cancer (EC) is a common leading cause of cancer-related death in women, which is associated with the increased level of estrogen in the body. Artesunate (ART), an active compound derived from Artemisia annua L., exerted antitumor properties in several cancer types. However, the role of artesunate and the molecular basis on EC remains unclear. Here, we aimed to explore the effects and mechanisms of artesunate. Our results identified that estrogen receptor-α (ER-α) was a key factor for the type I EC (ER-α-positive), which might suppress the downstream LKB1/AMPK/mTOR pathway. Besides, we found ART significantly inhibited tumor proliferation in a dose-dependent manner. Mechanistic studies identified that ART led to tumor cell apoptosis and cell cycle arrest by downregulating the ER-α expression and activating the LKB1/AMPK/mTOR pathway. In addition, we found ART could increase the expression of heart and neural crest derivatives expressed 2 (HAND2) in the ER-α-positive EC cells, which could interact with ER-α. Through the gain-and loss-function experiments, we showed that over expression of HAND2 repressed the proliferation and migration of ER-α-positive EC cells via inhibition of ER-α expression. HAND2 knockdown increased ER-α expression and alleviated the antitumor effect of ART in vitro and in vivo. Overall, our study first showed that ART could be an effective antitumor agent through modulating ER-α-mediated LKB1/AMPK/mTOR pathway in the HAND2 dependent manner. Our findings provide an effective therapeutic agent for ER-α-positive EC treatment.

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“…Adiponectin has also been linked with breast cancer progression but has shown mostly anti-tumorigenic effects [ 170 , 171 , 172 , 173 , 174 ]. The effect on breast cancer progression seems to depend on ER status [ 170 ]. With increasing BMI, the levels of adiponectin in serum decreases [ 175 ].…”

Section: Breast Cancer Progression and Local Obesity-associated Biomarkersmentioning

confidence: 99%

Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

Holm

Rosendahl

Borgquist

2021

Cancers

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Obesity is associated with an increased risk of breast cancer, which is the most common cancer in women worldwide (excluding non-melanoma skin cancer). Furthermore, breast cancer patients with obesity have an impaired prognosis. Adipose tissue is abundant in the breast. Therefore, breast cancer develops in an adipose-rich environment. During obesity, changes in the local environment in the breast occur which are associated with breast cancer. A shift towards a pro-inflammatory state is seen, resulting in altered levels of cytokines and immune cells. Levels of adipokines, such as leptin, adiponectin, and resistin, are changed. Aromatase activity rises, resulting in higher levels of potent estrogen in the breast. Lastly, remodeling of the extracellular matrix takes place. In this review, we address the current knowledge on the changes in the breast adipose tissue in obesity associated with breast cancer initiation and progression. We aim to identify obesity-associated biomarkers in the breast involved in the interplay between obesity and breast cancer. Hereby, we can improve identification of women with obesity with an increased risk of breast cancer and an impaired prognosis. Studies investigating mammary adipocytes and breast adipose tissue in women with obesity versus women without obesity are, however, sparse and further research is needed.

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Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression

Cited by 17 publications

References 175 publications

The Importance of Breast Adipose Tissue in Breast Cancer

The Importance of Breast Adipose Tissue in Breast Cancer

Artesunate Suppresses the Proliferation and Development of Estrogen Receptor-α-Positive Endometrial Cancer in HAND2-Dependent Pathway

Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

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