S100A4 downregulates filopodia formation through increased dynamic instability

Goh, Connie; Hersch, Nils; Rudland, Philip S.; Barraclough, Roger; Hoffmann, Bernd; Gross, Stephane R.

doi:10.4161/cam.5.5.17773

Cited by 10 publications

(16 citation statements)

References 42 publications

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“…Consequently, the biological functions of S100A4 have primarily been studied in cancer systems, whether cellular or animal. S100A4 expression can provoke increased motility and invasion in cancer cell lines originating from breast, colorectal, pancreatic, lung and esophageal squamous epithelia to list just a few recently published contributions [61][62][63][64][65][66][67][68][69].…”

Section: S100a4mentioning

confidence: 99%

Joining S100 proteins and migration: for better or for worse, in sickness and in health

Gross

Sin

Barraclough

et al. 2013

Cell. Mol. Life Sci.

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153

148

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The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used.

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Section: S100a4mentioning

confidence: 99%

Joining S100 proteins and migration: for better or for worse, in sickness and in health

Gross

Sin

Barraclough

et al. 2013

Cell. Mol. Life Sci.

Self Cite

153

148

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“…Expression of S100A4 has been correlated to significant changes in overall actin organisation and cellular extensions, with extensive increases in lamellipodia and forward protrusions [104,105] which, in turn, are thought to result in greatly enhanced cellular motility. Similarly, S100A4 has been found to be enriched at both the leading edge and in pseudopodia of migrating cells [104,106].…”

Section: S100a4 Regulates Cellular Protrusionmentioning

confidence: 99%

“…The true involvement of S100A4 in the regulation of liprin and/or formin activities is currently missing, but one could hypothesise that the three protein functions may be intertwined. Given that S100A4 expression has been linked to filopodia instability [105], and the critical known role of formins in the process [58], one could for instance speculate and put forward a new forminliprin-dependent function for this small calcium-binding protein.…”

Section: S100a4 Regulates Cellular Protrusionmentioning

confidence: 99%

“…Although direct evidence of S100A4 being localised in the lamella of migrating cells is still lacking, numerous reports have highlighted potential regulatory functions of the S100A4 within this subcellular fraction since its expression has been shown to lead to dramatic changes in numbers and organisation of focal adhesions and actin stress fibres [104,105,109,122,128,136]. I will briefly discuss here the different properties that S100A4 encompasses towards a remodelling of this cellular architecture.…”

Section: S100a4 Functions In the Lamellum And Cellular Contractionsmentioning

confidence: 99%

“…Although myosin is not physically present in the adhesion, it influences the process through its attachment to actin bundles with which adhesion is associated [79]. Whilst no direct evidence has been presented to demonstrate that S100A4 interacting with the myosin network results in the loss of adhesion of cells with their substratum, there is a compelling number of reports which have linked S10A4 expression to either stress fibre losses or reduction of focal adhesion stability or maturation [104,105,109,122,128,136]. Similarly, regulating the assembly status of myosin via phosphorylation of sites in the C-terminal coiled coil and tailpiece regions have also been associated with reorganisation of the cytoskeleton and focal adhesions.…”

Section: S100a4 Functions In the Lamellum And Cellular Contractionsmentioning

confidence: 99%

See 2 more Smart Citations

The Actomyosin Network and Cellular Motility: A S100A4 Regulatory View into the Process

Gross¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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Cell migration is a fundamental process responsible for numerous physiological and physiopathological conditions such as inflammation, embryogenesis and cancer. This central aspect of cell biology has seen quantum leaps in our understanding of the coordinated regulations, both spatial and temporal of numerous cytoskeletal proteins and their orchestrations. At the molecular level, this dynamic cellular process can be naively summarised as an engineered cycle composed of three distinct phases of (1) formation of cellular protrusion to initiate contact followed by (2) the adhesion with the external environment/cell-extracellular established connection and (3) the actomyosin force generation to consequently remodel the cytoskeleton. A prominent factor that regulates cellular motility is S100A4, a protein that has received constant attention for its significant role in cellular migration. Consequently, and in order to focus further the impact of this work, the present chapter aims to review some of the actomyosin proteins/complexes that have been demonstrated to be crucial players of the cyclic migration process but are also S100A4 interactors. In doing so, this chapter aims to capture a picture of how expression of this small, calcium-binding protein may, in essence, remodel at different levels the actin organisation and fulfil the motility engineered cycle of protrusion, attachments and contractions.Other than these physiological conditions, cellular motility is essential in regulating some of the physiopathological steps seen in disease. As example, it is well-documented that cellular migration is one of the prominent factors involved in the later stages of carcinogenesis and the subsequent phases of metastasis [9][10][11]. Cancer cell dissemination is clearly dependent upon the ability of migratory tumour cells to evade away from their initial niche, leading to the colonisation and formation of distant secondary lesions in the body [12].At the molecular level, cell migration requires the coordinated regulations, both spatial and temporal of numerous cytoskeletal proteins, to orchestrate the dynamic cellular processes needed for cells to acquire movement. In this context, the actin cytoskeleton and the closely linked myosin network play essential functions [13,14]. The process of cellular motility can be summarised as an engineered cycle composed of three distinct phases which are, (1) formation of cellular protrusion in the forms of lammelipodia and fillopodia to initiate contact and adhesion with the external environment, (2) regulation of cell-extracellular matrix established connections, usually integrin-dependent, and (3) force generation by the actomyosin network which will control both the structure and organisation of the motile architecture [15]. I provide here a brief overview of some of the different elements and protein complexes that are regulated during this migratory cycle, focusing primarily on specific components of the actomyosin complexes.A group of low-molecular weight polypeptides that has been...

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S100P enhances the motility and invasion of human trophoblast cell lines

Tabrizi

Lancaster

Ismail

et al. 2018

Sci Rep

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S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.

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S100A4 downregulates filopodia formation through increased dynamic instability

Cited by 10 publications

References 42 publications

Joining S100 proteins and migration: for better or for worse, in sickness and in health

Joining S100 proteins and migration: for better or for worse, in sickness and in health

The Actomyosin Network and Cellular Motility: A S100A4 Regulatory View into the Process

S100P enhances the motility and invasion of human trophoblast cell lines

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