A Polymorphic Variant of AFAP-110 Enhances cSrc Activity

Clump, David A.; Yu, Jing; Cho, Youngjin; Gao, Rui; Jett, John E.; Zot, Henry G.; Cunnick, Joan E.; Snyder, Brandi; Clump, Anne C.; Dodrill, Melissa; Gannett, Peter M.; Coad, James E.; Shurina, Robert D.; Figg, William D.; Reed, Eddie; Flynn, Daniel C.

doi:10.1593/tlo.10106

Cited by 3 publications

(2 citation statements)

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“…Considering that AFAP1 interacts with cSrc ( 8 , 11 , 35 ), we examined the effect of the loss of AFAP1 on cSrc activity in mammary glands. To measure cSrc activity, we prepared whole tissue lysates from both WT and KO mammary glands from mice at 8 weeks of age, P16.5 and L3.…”

Section: Resultsmentioning

confidence: 99%

Actin filament-associated protein 1 is required for cSrc activity and secretory activation in the lactating mammary gland

et al. 2014

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Actin filament-associated protein 1 (AFAP1) is an adaptor protein of cSrc that binds to filamentous actin and regulates the activity of this tyrosine kinase to affect changes to the organization of the actin cytoskeleton. In breast and prostate cancer cells, AFAP1 has been shown to regulate cellular responses requiring actin cytoskeletal changes such as adhesion, invadopodia formation and invasion. However, a normal physiological role for AFAP1 has remained elusive. In this study, we generated an AFAP1 knockout mouse model that establishes a novel physiological role for AFAP1 in lactation. Specifically, these animals displayed a defect in lactation that resulted in an inability to efficiently nurse. Histologically, the mammary glands of the lactating knockout mice were distinguished by the accumulation of large cytoplasmic lipid droplets in the alveolar epithelial cells. There was a reduction in lipid synthesis and the expression of lipogenic genes without a corresponding reduction in the production of beta-casein, a milk protein. Furthermore, these defects were associated with histological and biochemical signs of precocious involution. This study also demonstrated that AFAP1 responds to prolactin, a lactogenic hormone, by forming a complex with cSrc and becoming tyrosine phosphorylated. Together, these observations pointed to a defect in secretory activation. Certain characteristics of this phenotype mirrored the defect in secretory activation in the cSrc knockout mouse, but most importantly, the activity of cSrc in the mammary gland was reduced during early lactation in the AFAP1 null mouse and the localization of active cSrc at the apical surface of luminal epithelial cells during lactation was selectively lost in the absence of AFAP1. These data define, for the first time, the requirement of AFAP1 for the spatial and temporal regulation of cSrc activity in the normal breast, specifically for milk production.

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Section: Resultsmentioning

confidence: 99%

Actin filament-associated protein 1 is required for cSrc activity and secretory activation in the lactating mammary gland

et al. 2014

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“…AFAP1-AS1 is one of the lncRNAs located on the anti-sense strand of protein-coding gene AFAP1. AFAP1 is a kind of motor fiber-related protein, which acts as an adapter molecule to link to other proteins, such as SRC and PKC, to modulate changes in actin filament integrity, and to influence the cytophagy, cell movement, tumor invasion, and metastasis 33 – 36 and the AFAP1-AS1 exon 2 and AFAP1 exons 14, 15, and 16 are just overlapping and complementary regions. 19 …”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA AFAP1-AS1, a potential novel biomarker to predict the clinical outcome of cancer patients: a meta-analysis

Liu

Xue

Zhu

et al. 2016

OTT

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A number of studies have demonstrated that the expression level of actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) was upregulated in various cancers. High expression of AFAP1-AS1 is associated with an increased risk of metastasis and a poor prognosis in cancer patients. The electronic search was conducted in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang database. We collected relevant articles to explore the association between the expression levels of AFAP1-AS1 and lymph node metastasis, distant metastasis, overall survival, relapse-free survival, and progression-free survival. A total of 1,017 patients from eight studies were finally included. The results showed that cancer patients with high AFAP1-AS1 expression suffered an increased risk of developing lymph node metastasis (odds ratio =3.19, 95% confidence interval [CI]: 2.11–4.83, P<0.00001) and distant metastasis (odds ratio =3.05, 95% CI: 1.84–5.04, P<0.0001). Moreover, we found that patients with high AFAP1-AS1 expression also had a poorer overall survival (hazard ratio [HR]: 1.98, 95% CI: 1.57–2.38, P=0.000), a worse progression-free survival (HR: 1.73, 95% CI: 1.11–2.35, P=0.000), and a shorter recurrence-free survival (HR: 1.96, 95% CI: 1.02–2.90, P=0.000) than those with low AFAP1-AS1 expression. High expression of AFAP1-AS1 was associated with poor clinical outcome. AFAP1-AS1 might serve as a potential novel biomarker for indicating the clinical outcomes in human cancers.

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Degrading Devices: Invadosomes in Proteolytic Cell Invasion

Linder

Wiesner

Himmel

2011

Annu. Rev. Cell Dev. Biol.

337

425

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Podosomes and invadopodia, collectively known as invadosomes, are cell-matrix contacts in a variety of cell types, such as monocytic cells or cancer cells, that have to cross tissue barriers. Both structures share an actin-rich core, which distinguishes them from other matrix contacts, and are regulated by a multitude of signaling pathways including RhoGTPases, kinases, actin-associated proteins, and microtubule-dependent transport. Invadosomes recruit and secrete proteinases and are thus able to lyse extracellular matrix components. They are therefore considered to be potential key structures in proteolytic cell invasion in both physiological and pathological settings. This review provides an overview of the field, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadosomes in 3D environments and in vivo.

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A Polymorphic Variant of AFAP-110 Enhances cSrc Activity

Cited by 3 publications

References 34 publications

Actin filament-associated protein 1 is required for cSrc activity and secretory activation in the lactating mammary gland

Actin filament-associated protein 1 is required for cSrc activity and secretory activation in the lactating mammary gland

Long noncoding RNA AFAP1-AS1, a potential novel biomarker to predict the clinical outcome of cancer patients: a meta-analysis

Degrading Devices: Invadosomes in Proteolytic Cell Invasion

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