Actin-bundling proteins in cancer progression at a glance

Stevenson, Richard P.; Veltman, Douwe M.; Machesky, Laura M.

doi:10.1242/jcs.093799

Cited by 135 publications

(126 citation statements)

References 105 publications

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“…25 The ability of cells to extend their apical end in order to become motile is a result of reorganization of the macro-, intermediate-and/or micro-filaments. 26 This process can further be facilitated by various stimuli including physical space (wound) as well as tumor microenvironment. Here, using confocal microscopy, in the presence of a stimulus, we confirmed that a decrease in MIEN1 protein interferes with the ability of OSC-2 cells to form filopodia protrusions, an event required during cell-cell adhesion and cell motility.…”

Section: Discussionmentioning

confidence: 99%

MIEN1 promotes oral cancer progression and implicates poor overall survival

Rajendiran

Kpetemey

Maji

et al. 2015

Cancer Biology & Therapy

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Abbreviations: CRS, current reformed smoker; CS, current smoker; GFP, green fluorescent protein; HNSCC, head and neck squamous cell carcinoma; MIEN1, migration and invasion enhancer 1; MMP-9, matrix metallopeptidase 9; NF-kB, nuclear factor kappalight-chain-enhancer of activated B cells; OSCC, oral squamous cell carcinoma; siRNA, small interfering RNA; TCGA, the cancer genome atlas; uPA, urokinase plasminogen activator; VEGF, vascular endothelial growth factorOral squamous cell carcinoma is a highly malignant tumor with the potential to invade local and distant sites and promote lymph node metastasis. Major players underlying the molecular mechanisms behind tumor progression are yet to be fully explored. Migration and invasion enhancer 1 (MIEN1), a novel protein overexpressed in various cancers, facilitates cell migration and invasion. In the present study we investigated the expression and role of MIEN1 in oral cancer progression using an in vitro model, patient derived oral tissues and existing TCGA data. Expression analysis using immortalized normal and cancer cells demonstrated increased expression of MIEN1 in cancer. Assays performed after MIEN1 knockdown in OSC-2 cells showed decreased migration, invasion and filopodia formation; while MIEN1 overexpression in DOK cells increased these characteristics and also up-regulated some Akt/NF-kB effectors, thereby suggesting an important role for MIEN1 in oral cancer progression. Immunohistochemical staining and analyses of oral tissue specimens, collected from patients over multiple visits, revealed significantly more staining in severe dysplasia and squamous cell carcinoma compared to mildly dysplastic or hyperplastic tissues. Finally, this was corroborated with the TCGA dataset, where MIEN1 expression was not only higher in intermediate and high grade cancer with significantly lower survival but also correlated with smoking. In summary, we demonstrate that MIEN1 expression not only positively correlates with oral cancer progression but also seems to be a critical molecular determinant in migration and invasion of oral cancer cells, thereby, playing a possible role in their metastatic dissemination.

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Section: Discussionmentioning

confidence: 99%

MIEN1 promotes oral cancer progression and implicates poor overall survival

Rajendiran

Kpetemey

Maji

et al. 2015

Cancer Biology & Therapy

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“…Both protrusions arise from an underlying dendritic network of branched actin filaments by means of actin bundles, which provide force to push the membrane (1,2,10,11).…”

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confidence: 99%

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Audenhove¹,

Denert²,

Boucherie³

et al. 2016

Journal of Biological Chemistry

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Invadopodia and filopodia are dynamic, actin-based protrusions contributing to cancer cell migration, invasion, and metastasis. The force of actin bundles is essential for their protrusive activity. The bundling protein fascin is known to play a role in both invadopodia and filopodia. As it is more and more acknowledged that functionally related proteins cooperate, it is unlikely that only fascin bundles actin in these protrusions. Another interesting candidate is L-plastin, normally expressed in hematopoietic cells, but considered a common marker of many cancer types. We identified L-plastin as a new component of invadopodia, where it contributes to degradation and invasiveness. By means of specific, high-affinity nanobodies inhibiting bundling of fascin or L-plastin, we further unraveled their cooperative mode of action. We show that the bundlers cannot compensate for each other due to strikingly different bundling characteristics: L-plastin bundles are much thinner and less tightly packed. Composite bundles adopt an intermediate phenotype, with fascin delivering the rigidity and strength for protrusive force and structural stability, whereas L-plastin accounts for the flexibility needed for elongation. Consistent with this, elevated L-plastin expression promotes elongation and reduces protrusion density in cells with relatively lower L-plastin than fascin levels.Filopodia are finger-like protrusions coordinating movement at the cell front by "sensing" extracellular stimuli (1). Invadopodia on the other hand are formed at the ventral cell side, enabling matrix degradation by localized proteolysis (2). As both actin-based protrusions contribute to migration and invasion, they are associated with cancer metastasis (3, 4), which has also been shown in vivo (5, 6).The architecture and dynamics of filopodia and invadopodia are controlled by a broad variety of actin-binding proteins (7,8). Moreover, these regulating proteins show highly similar spatial and temporal distributions in filopodia and invadopodia (9).

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“…Many actin-bundling proteins are also linked to cancer progression and tumor chemoresistance [63]. Fascin proteins organize F-actin into parallel bundles and are required for the formation of actin-based cellular protrusions.…”

Section: The Cytoskeleton and Its Role In Cancer Progressionmentioning

confidence: 99%

Novel Insights into the Role of the Cytoskeleton in Cancer

Zhang¹,

Pei²,

Ji³

et al. 2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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The cytoskeleton is a complex network of highly ordered intracellular ilaments that plays a central role in controlling cell shape, division, functions, and interactions in human organs and tissues, but dysregulation of this network can contribute to numerous human diseases, including cancer. To clarify the various functions of the cytoskeleton and its role in cancer progression, in this chapter, we will discuss the microilament (actin cytoskeleton), microtubule (β-tubulin), and intermediate ilament (keratins, cytokeratins, vimentin, and lamins) cytoskeletal structures; analyze the physiological functions of the cytoskeleton and its regulation of cell diferentiation; and investigate the roles of the cytoskeleton in cancer progression, the epithelial-mesenchymal transition process (EMT), and the mechanisms of multidrug resistance (MDR) in relation to the cytoskeleton. Importantly, the cytoskeleton, as a key regulator of the transcription and expression of many genes, is known to be involved in various physiological and pathological processes, which makes the cytoskeleton a novel and highly efective target for assessing the response to antitumor therapy in cancer.Keywords: Cytoskeleton, Regulator, cell diferentiation, drug resistance, EMT IntroductionThe cytoskeleton is a structure similar to a bird's nest; it can be tightly packed or sparse and is found in both prokaryotes and eukaryotes [1]. The main component of the cytoskeleton is protein, and the speciic diferences in structure never afect the type of proteins incorporated [2]. The cytoskeletons of prokaryotes display apparent plasticity in composition, without conservation of the core ilament-forming proteins. However, the eukaryotic cytoskeleton has evolved in a variety of functions through the addition of accessory proteins and extensive There are three main cytoskeletal structures in eukaryotes, microilaments (MFs, ≈7 nm diameter), microtubules (MTs, ≈25 nm diameter), and intermediate ilaments (IFs, ≈10 nm diameter) [1]. MFs are responsible for cell contraction and reinforcement of the cell surface and allow changes in cell morphology. Actin and tubulin are the main globular proteins that form MFs and MTs, respectively. Actin is a ubiquitous eukaryotic ilament-forming protein. Actin ilaments (also called microilaments or F-actin) consist of two proto ilament polymers wound together in a right-handed helix [3]. Eukaryotic actin is a member of a large and diverse superfamily of ATPases that includes Hsp70 chaperones and several classes of sugar/sugar alcohol kinases [4,5] as well as eukaryotic actin-related proteins (ARPs) [6,7]. The actin cytoskeleton is involved in actin-based cytoskeletal structures, including various functionally distinct structures of actin organization, and can be regulated by actin regulatory proteins. It is well known that the actin cortex consists of a dense mesh-like array of F-actin anchored to the cell membranes [8,9]. This structure provides the core "skeleton" of the cell, functioning to deine cell shape and provi...

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Actin-bundling proteins in cancer progression at a glance

Cited by 135 publications

References 105 publications

MIEN1 promotes oral cancer progression and implicates poor overall survival

MIEN1 promotes oral cancer progression and implicates poor overall survival

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Novel Insights into the Role of the Cytoskeleton in Cancer

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