Paxillin, a novel controller in the signaling of estrogen to FAK/N-WASP/Arp2/3 complex in breast cancer cells

Shortrede, Jorge Eduardo; Uzair, Ivonne Denise; Neira, Flavia Judith; Flamini, Marina Inés; Sanchez, Angel Matías

doi:10.1016/j.mce.2016.04.007

Cited by 29 publications

(24 citation statements)

References 43 publications

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“…Significant changes in actin organization with pseudopodia and membrane ruffles formation became visible from 10 −8 M for all androgens assayed (Figure 2 ). As we have shown in previous report ( 18 , 19 ), E2 10 −9 M was used as positive control of actin filaments remodeling.…”

Section: Resultsmentioning

confidence: 99%

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Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

et al. 2016

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The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin–radixin–moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen – DHT – only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment.

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Section: Resultsmentioning

confidence: 99%

“…The main finding of this study is that androgens modulate actin cytoskeleton rearrangement in T47D cells, thereby influencing cell migration and invasion. A precise regulation of actin dynamics is necessary for cell migration, which is required for cancer spread, invasion, and metastasis ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

et al. 2016

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“…Cytoskeletal components such as actin and tubulin play important roles in migration and invasion, notably in the pathology of tumour cells ( Shortrede et al, 2016 ). Actin takes two forms: monomeric globular (G-actin) and filamentous (F-actin).…”

Section: Introductionmentioning

confidence: 99%

PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Cummins

Bozatzi

et al. 2018

Journal of Cell Science

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Our previous studies of PAWS1 (protein associated with SMAD1; also known as FAM83G) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1-knockout U2OS osteosarcoma cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration. Genetic ablation of CD2AP from U2OS cells instigates actin and cell migration defects reminiscent of those seen in PAWS1-knockout cells.This article has an associated First Person interview with the first authors of the paper.

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“…Cancer cell motility and migration are critical steps needed to accomplish invasion and metastasis ( 16 ). Regulation of the actin cytoskeleton is key in this process; it is a tightly regulated event ( 17 ). In the presence of LH or FSH, the actin-binding protein moesin and the focal adhesion complex regulator focal adhesion kinase (FAK) are phosphorylated and then localize to the plasma membrane, where they endow cells with higher motility through increased adhesion to the extracellular matrix ( 15 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

“…In the presence of LH or FSH, the actin-binding protein moesin and the focal adhesion complex regulator focal adhesion kinase (FAK) are phosphorylated and then localize to the plasma membrane, where they endow cells with higher motility through increased adhesion to the extracellular matrix ( 15 , 18 ). This is mostly driven by the recruitment of large intracellular protein complexes, such as the paxillin/cortactin/N-WASP-Arp2/3 complex, which promote the formation of molecular bridges between actin, integrins, and focal adhesion complexes at specialized cell membrane sites involved in cellular motility ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Regulatory Actions of LH and Follicle-Stimulating Hormone on Breast Cancer Cells and Mammary Tumors in Rats

et al. 2018

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Gonadotrophins are mainly known to influence the body through the formation of gonadal steroids. However, receptors for luteinizing hormone (LH) and follicular-stimulating hormone (FSH) are present in a set of extra-gonadal tissues in humans and animals, but their functional relevance is uncertain. In this article, we present experimental evidence that, in T-47D breast cancer (BC) cells, FSH, and LH alter the expression of genes involved in adhesion, motility, and invasion through the activation of their receptors. Using miniarray technology we also found that LH influences the expression of a broad set of genes involved in cancer biology in T-47D cells. Interestingly, the regulatory actions of FSH and LH depend on the modality of exposure, with significant differences between pre-pubertal-like vs. post-menopausal-like amounts of gonadotrophins, but not after intermittent administration, representative of fertile life. We also studied the modulation of the circulating levels of gonadotrophins in an in vivo rat model of BC progression and observed a direct correlation with the extent of cancer growth. These results support the hypothesis that gonadotrophins may have direct effects on extra-gonadal tissues. They also highlight that gonadotrophins could potentially contribute to BC progression, particularly in post-menopausal women who typically have higher gonadotrophin levels. This research may ultimately lead to testing the use of gonadotrophin-modulating drugs in BC patients.

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Paxillin, a novel controller in the signaling of estrogen to FAK/N-WASP/Arp2/3 complex in breast cancer cells

Cited by 29 publications

References 43 publications

Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Regulatory Actions of LH and Follicle-Stimulating Hormone on Breast Cancer Cells and Mammary Tumors in Rats

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