Effects of the scaffold proteins liprin‐α1, β1 and β2 on invasion by breast cancer cells

Chiaretti, Sara; Astro, Veronica; Chiricozzi, Elena; Curtis, Iván de

doi:10.1111/boc.201500063

Cited by 31 publications

(46 citation statements)

References 27 publications

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“…Secretory trafficking delivers to the cell surface membrane type 1 metalloprotease (MT1-MMP), which can degrade the extracellular matrix around FAs, resulting in integrin detachment, loss of tension, and FA turnover 116 . These observations help to explain why liprin-α1, liprin-β1, LL5β, and ELKS promote invasive behavior and internalization of integrins in breast cancer cells 86, 88, 117– 119 . Importantly, MT1-MMP delivery and integrin recycling also strongly depend on endosomal trafficking, which requires microtubules (for review, see 120, 121).…”

Section: Clasp- and Ll5-associated Complexes In Microtubule Organizatmentioning

confidence: 75%

Linking cortical microtubule attachment and exocytosis

Noordstra

Akhmanova

2017

F1000Res

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Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.

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Section: Clasp- and Ll5-associated Complexes In Microtubule Organizatmentioning

confidence: 75%

Linking cortical microtubule attachment and exocytosis

Noordstra

Akhmanova

2017

F1000Res

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“…Matrix composition, stiffness, diffusion limitations, and vasculature are the primary contributors to drug resistance caused by the physical attributes of the ECM. In the case of CAM‐DR, the binding of cancer and/or stromal cells to ECM ligands such as collagens and fibronectin alters the mechanical properties of the matrix and can activate pro‐survival pathways, most commonly mediated by β1 integrins (Chiaretti, Astro, Chiricozzi, & de Curtis, 2016; Dittmer & Leyh, 2015; Park et al, 2006). SFM‐DR is caused by growth factors, proteins, proteases, and cytokines secreted by cancer‐associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), or tumor‐associated macrophages.…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional culture models to study drug resistance in breast cancer

Fisher

Rao

2020

Biotech & Bioengineering

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Despite recent advances in breast cancer treatment, drug resistance frequently presents as a challenge, contributing to a higher risk of relapse and decreased overall survival rate. It is now generally recognized that the extracellular matrix and cellular heterogeneity of the tumor microenvironment influences the cancer cells' ultimate fate. Therefore, strategies employed to examine mechanisms of drug resistance must take microenvironmental influences, as well as genetic mutations, into account. This review discusses three‐dimensional (3D) in vitro model systems which incorporate microenvironmental influences to study mechanisms of drug resistance in breast cancer. These bioengineered models include spheroid‐based models, biomaterial‐based models such as polymeric scaffolds and hydrogels, and microfluidic chip‐based models. The advantages of these model systems over traditionally studied two‐dimensional tissue culture polystyrene are examined. Additionally, the applicability of such 3D models for studying the impact of tumor microenvironment signals on drug response and/or resistance is discussed. Finally, the potential of such models for use in the development of strategies to combat drug resistance and determine the most promising treatment regimen is explored.

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“…The mammalian liprin family includes four liprin-α (liprin-α1 to -α4) proteins and two liprin-β (β1 and β2) proteins [8], which together form heterodimers and act as scaffolds [9]. A number of recent studies have revealed broader functions of the liprin family in regulating the development and homeostasis in other organs, including the mammary gland and lymphatic vessel [10,11]. Notably, analysis of human cancers has revealed dysfunctions of the liprin proteins, with evidence pointing to the different roles of liprin family members in distinct aspects of tumor biology.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, analysis of human cancers has revealed dysfunctions of the liprin proteins, with evidence pointing to the different roles of liprin family members in distinct aspects of tumor biology. For example, overexpression of liprin-α1 promotes breast cancer cell invasion by regulating lamellipodia stability and integrin-mediated focal adhesions [10,12]. By contrast, liprin-β2 impairs cell motility and suppresses tumor invasion, which is indicative of its role as a tumor suppressor [10].…”

Section: Introductionmentioning

confidence: 99%

Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage

Jiao

2019

ARCH BIOL SCI BELGRA

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Liprin-β1 is one of the broadly-expressed liprin family members. Dysregulation of liprin-β1 has been implicated in several types of human cancers. However, the expression of liprin-β1 and its clinicopathological significance in human hepatocellular carcinoma (HCC) remains elusive. We evaluated the protein expression of liprin-β1 in HCC and non-tumor liver tissues by immunohistochemistry, and investigated the relationship between liprin-β1 expression and the clinicopathological attributes of HCC. We found that liprin-β1 expression was significantly higher in HCC than in non-tumor liver tissues. Further analysis showed that higher levels of liprin-β1 in HCC were significantly associated with the advanced clinical stage. Interestingly, liprin-β1 was not detected in cholangiocellular carcinoma specimens. These findings suggest that an elevated expression of liprin-β1 may be involved in HCC progression, providing the rationale that upregulation of liprin-β1 may serve as a novel biomarker for human HCC.

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Effects of the scaffold proteins liprin‐α1, β1 and β2 on invasion by breast cancer cells

Abstract: Our results indicate the importance of liprins in breast cancer cell invasion, and are expected to lead to future investigations on the mechanisms underlying the effects of distinct liprin proteins in different processes linked to tumor cell migration and invasion.

Cited by 31 publications

References 27 publications

Linking cortical microtubule attachment and exocytosis

Linking cortical microtubule attachment and exocytosis

Three‐dimensional culture models to study drug resistance in breast cancer

Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage

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