The Complex Genetic Basis and Multilayered Regulatory Control of Yeast Pseudohyphal Growth.

Eukaryotic cells are exquisitely responsive to external and internal cues, achieving precise control of seemingly diverse growth processes through a complex interplay of regulatory mechanisms. The budding yeast Saccharomyces cerevisiae provides a fascinating model of cell growth in its stress-responsive transition from planktonic single cells to a filamentous pseudohyphal growth form. During pseudohyphal growth, yeast cells undergo changes in morphology, polarity, and adhesion to form extended and invasive multicellular filaments. This pseudohyphal transition has been studied extensively as a model of conserved signaling pathways regulating cell growth and for its relevance in understanding the pathogenicity of the related opportunistic fungus Candida albicans, wherein filamentous growth is required for virulence. This review highlights the broad gene set enabling yeast pseudohyphal growth, signaling pathways that regulate this process, the role and regulation of proteins conferring cell adhesion, and interesting regulatory mechanisms enabling the pseudohyphal transition.

Invasion of the stigma by oomycete pathogenic hyphae or pollen tubes: striking similarities and differences.

Both the pollen tube and hyphae of filamentous pathogens penetrate the outer layer of the host and then grow within host tissues. Early epidermal responses are decisive for the outcome of these two-cell interaction processes. We identified a single cell type, the papilla in the stigma of Arabidospis, as a tool to conduct a comprehensive comparative analysis on how an epidermal cell responds to the invasion of an unwanted pathogen or a welcome pollen tube. We showed that Phytophtora parasitica, a root oomycete, effectively breaches the stigmatic cell wall and develops as a biotroph within the papilla cytoplasm. These invasive features resemble the behaviour exhibited by the pathogen within its natural host cell, but diverge from the manner in which the pollen tube progresses, being engulfed within the papilla cell wall. Quantitative analysis revealed that both invaders trigger reorganization of the stigmatic endomembrane system and the actin cytoskeleton. While some remodelling processes are shared between the two interactions, others appear more specific towards the respective invader. These findings underscore the remarkable ability of an epidermal cell to differentiate between two types of invaders, thereby enabling it to trigger the most suitable response during the onset of invasion.

Differentially expressed extracellular matrix genes functionally separate ameloblastoma from odontogenic keratocyst.

BACKGROUND: Ameloblastoma and odontogenic keratocyst (OKC) are odontogenic tumors that develop from remnants of odontogenic epithelium. Both display locally invasive growth characteristics and high predilection for recurrence after surgical removal. Most ameloblastomas harbor BRAFV600E mutation while OKCs are associated with PATCH1 gene mutation but distinctive indicators of ameloblastoma growth characteristics relative to OKC are still unclear. The aim of this study was to assess hub genes that underlie ameloblastoma growth characteristics using bioinformatic analysis, ameloblastoma samples and mouse xenografts of human epithelial-derived ameloblastoma cells. METHODS: RNA expression profiles were extracted from GSE186489 gene expression dataset acquired from Gene Expression Ominibus (GEO) database. Galaxy and iDEP online analysis tools were used to identify differentially expressed genes that were further characterized by gene ontology (GO) and pathway analysis using ShineyGO. The protein-protein interaction (PPI) network was constructed for significantly upregulated differentially expressed genes using online database STRING. The PPI network visualization was performed using Cytoscape and hub gene identification with cytoHubba. Top ten nodes were selected using maximum neighborhood component, degree and closeness algorithms and analysis of overlap was performed to confirm the hub genes. Epithelial-derived ameloblastoma cells from conventional ameloblastoma were transplanted into immunocompromised mice to recreate ameloblastoma in vivo based on the mouse xenograft model. The top 3 hub genes FN1, COL I and IGF-1 were validated by immunostaining and quantitative analysis of staining intensities to ameloblastoma, OKC samples and mouse ameloblastoma xenografts tissues. RESULTS: Seven hub genes were identified among which FN1, COL1A1/COL1A2 and IGF-1 are associated with extracellular matrix organization, collagen binding, cell adhesion and cell surface interaction. These were further validated by positive immunoreactivity within the stroma of ameloblastoma samples but both ameloblastoma xenograft and OKC displayed only FN1 and IGF-1 immunoreactivity while COL 1 was unreactive. The expression levels of both FN1 and IGF-1 were much lower in OKC relative to ameloblastoma. CONCLUSION: This study further validates a differentially upregulated expression of matrix proteins FN1, COL I and IGF-1 in ameloblastoma relative to OKC. It suggests that differential stromal architecture and growth characteristics of ameloblastoma relative to OKC could be an interplay of differentially upregulated genes in ameloblastoma.

How tissue fluidity influences brain tumor progression.

Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer.

Involvement of Mitochondrial Mechanisms and Cyclooxygenase-2 Activation in the Effect of Desethylamiodarone on 4T1 Triple-Negative Breast Cancer Line.

Novel compounds significantly interfering with the mitochondrial energy production may have therapeutic value in triple-negative breast cancer (TNBC). This criterion is clearly fulfilled by desethylamiodarone (DEA), which is a major metabolite of amiodarone, a widely used antiarrhythmic drug, since the DEA previously demonstrated anti-neoplastic, anti-metastasizing, and direct mitochondrial effects in B16F10 melanoma cells. Additionally, the more than fifty years of clinical experience with amiodarone should answer most of the safety concerns about DEA. Accordingly, in the present study, we investigated DEA's potential in TNBC by using a TN and a hormone receptor positive (HR+) BC cell line. DEA reduced the viability, colony formation, and invasive growth of the 4T1 cell line and led to a higher extent of the MCF-7 cell line. It lowered mitochondrial transmembrane potential and induced mitochondrial fragmentation. On the other hand, DEA failed to significantly affect various parameters of the cellular energy metabolism as determined by a Seahorse live cell respirometer. Cyclooxygenase 2 (COX-2), which was upregulated by DEA in the TNBC cell line only, accounted for most of 4T1's DEA resistance, which was counteracted by the selective COX-2 inhibitor celecoxib. All these data indicate that DEA may have potentiality in the therapy of TNBC.

Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines.

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114's anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug's anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential.

FvatfA regulates growth, stress tolerance as well as mycotoxin and pigment productions in Fusarium verticillioides.

FvatfA from the maize pathogen Fusarium verticillioides putatively encodes the Aspergillus nidulans AtfA and Schizasaccharomyces pombe Atf1 orthologous bZIP-type transcription factor, FvAtfA. In this study, a ΔFvatfA deletion mutant was constructed and then genetically complemented with the fully functional FvatfA gene. Comparing phenotypic features of the wild-type parental, the deletion mutant and the restored strains shed light on the versatile regulatory functions played by FvAtfA in (i) the maintenance of vegetative growth on Czapek-Dox and Potato Dextrose agars and invasive growth on unwounded tomato fruits, (ii) the preservation of conidiospore yield and size, (iii) the orchestration of oxidative (H2O2, menadione sodium bisulphite) and cell wall integrity (Congo Red) stress defences and (iv) the regulation of mycotoxin (fumonisins) and pigment (bikaverin, carotenoid) productions. Expression of selected biosynthetic genes both in the fumonisin (fum1, fum8) and the carotenoid (carRA, carB) pathways were down-regulated in the ΔFvatfA strain resulting in defected fumonisin production and considerably decreased carotenoid yields. The expression of bik1, encoding the polyketide synthase needed in bikaverin biosynthesis, was not up-regulated by the deletion of FvatfA meanwhile the ΔFvatfA strain produced approximately ten times more bikaverin than the wild-type or the genetically complemented strains. The abolishment of fumonisin production of the ΔFvatfA strain may lead to the development of new-type, biology-based mycotoxin control strategies. The novel information gained on the regulation of pigment production by this fungus can be interesting for experts working on new, Fusarium-based biomass and pigment production technologies. Key points • FvatfA regulates vegetative and invasive growths of F. verticillioides. • FvatfA also orchestrates oxidative and cell wall integrity stress defenses. • The ΔFvatfA mutant was deficient in fumonisin production. • FvatfA deletion resulted in decreased carotenoid and increased bikaverin yields.

Novel urokinase-plasminogen activator inhibitor SPINK13 inhibits growth and metastasis of hepatocellular carcinoma in vivo.

Advanced hepatocellular carcinoma (HCC) is a highly aggressive malignancy that is a serious threat to the public health system of China. Urokinase-plasminogen activator (uPA) can promote the invasive growth and metastasis of HCC cells by activating matrix metalloproteinases (MMPs), leading to the breakage of the extra-cellular matrix. uPA is a promising target for advanced HCC treatment. In this stuy the expression of uPA was examined by quantitative polymerase chain reaction in hepatic cell lines. Protein interaction between uPA and SPINK13 was identified by immunoprecipitation. In vitro biochemical assay was used to examine the inhibitory effect of the SPINK13 on the direct cleaving of the recombinant pro-MMP9 by uPA. The antitumor effect of SPINK13 was examined by transwell assay or the nude mice tumor model.The expression of uPA was much higher in highly aggressive HCC cell lines than in lowly aggressive HCC cell lines or non-tumor hepatic cell lines. SPINK13 interacted with uPA in HCC cells and directly inhibited the cleaving of MMP9 by uPA. Treatment of the recombinant SPINK13 protein inhibited the invasion of HCC cells in several experiments, such as transwell experiments or the intrahepatic growth model. The results of the study indicated that SPINK13 could function as a promising therapeutic approach for patients with advanced HCC.

HGF/c-MET Signaling in Melanocytes and Melanoma.

Hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-MET) signaling is involved in complex cellular programs that are important for embryonic development and tissue regeneration, but its activity is also utilized by cancer cells during tumor progression. HGF and c-MET usually mediate heterotypic cell⁻cell interactions, such as epithelial⁻mesenchymal, including tumor⁻stroma interactions. In the skin, dermal fibroblasts are the main source of HGF. The presence of c-MET on keratinocytes is crucial for wound healing in the skin. HGF is not released by normal melanocytes, but as melanocytes express c-MET, they are receptive to HGF, which protects them from apoptosis and stimulates their proliferation and motility. Dissimilar to melanocytes, melanoma cells not only express c-MET, but also release HGF, thus activating c-MET in an autocrine manner. Stimulation of the HGF/c-MET pathways contributes to several processes that are crucial for melanoma development, such as proliferation, survival, motility, and invasiveness, including distant metastatic niche formation. HGF might be a factor in the innate and acquired resistance of melanoma to oncoprotein-targeted drugs. It is not entirely clear whether elevated serum HGF level is associated with low progression-free survival and overall survival after treatment with targeted therapies. This review focuses on the role of HGF/c-MET signaling in melanoma with some introductory information on its function in skin and melanocytes.

Bevacizumab for Patients with Recurrent Multifocal Glioblastomas.

In patients with glioblastoma, antiangiogenic therapy with bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall survival (OS). Especially in patients with an unusual infiltrative phenotype as seen in multifocal glioblastoma, the use of BEV therapy is still more controversial. Therefore, we prepared a retrospective case series with 16 patients suffering from a multifocal glioblastoma treated with BEV. We compared these patients to a matched control cohort of 16 patients suffering from glioblastoma with a single lesion treated with BEV. The objective of this study was to evaluate whether the course of disease differs in glioblastoma patients with a multifocal disease pattern compared to those with a single lesion only. Patients were treated with BEV monotherapy or BEV in combination with irinotecan or lomustine (CCNU). Response rates and PFS were similar in both groups. There was a trend for an unfavorable OS in the patient group with multifocal glioblastoma, which was expected due to the generally worse prognosis of multifocal glioblastoma. We investigated whether BEV therapy affects the invasive growth pattern as measured by the appearance of new lesions on magnetic resonance imaging (MRI). Under BEV therapy, there was a trend for a lower frequency of new lesions both in multifocal and solitary glioblastoma. Based on these results, BEV therapy at relapse appears to be justified to no lesser extent in multifocal glioblastoma than in solitary glioblastoma.

Protein kinase A regulates gene-specific translational adaptation in differentiating yeast.

Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here we investigate translational reprogramming in yeast during cellular adaptation to the absence of glucose, a stimulus that induces invasive filamentous differentiation. Using ribosome footprint profiling and RNA sequencing to assay gene-specific translation activity genome-wide, we show that prolonged glucose withdrawal is accompanied by gene-specific changes in translational efficiency that significantly affect expression of the majority of genes. Notably, transcripts from a small minority (<5%) of genes make up the majority of translating mRNA in both rapidly dividing and starved differentiating cells, and the identities of these highly translated messages are almost nonoverlapping between conditions. Furthermore, these two groups of messages are subject to condition-dependent translational privilege. Thus the "housekeeping" process of translation does not stay constant during cellular differentiation but is highly adapted to different growth conditions. By comparing glucose starvation to growth-attenuating stresses that do not induce invasive filamentation, we distinguish a glucose-specific translational response mediated through signaling by protein kinase A (PKA). Together, these findings reveal a high degree of growth-state specialization of the translatome and identify PKA as an important regulator of gene-specific translation activity.

Ockham's razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) identifies a specific lung disorder characterized by chronic, progressive fibrosing interstitial pneumonia of unknown etiology, which lacks effective treatment. According to the current pathogenic perspective, the aberrant proliferative events in IPF resemble those occurring during malignant transformation. MAIN BODY: Receptor tyrosine kinases (RTK) are known to be key players in cancer onset and progression. It has been demonstrated that RTK expression is sometimes also altered and even druggable in IPF. One example of an RTK-the MET proto-oncogene-is a key regulator of invasive growth. This physiological genetic program supports embryonic development and post-natal organ regeneration, as well as cooperating in the evolution of cancer metastasis when aberrantly activated. Growing evidence sustains that MET activation may collaborate in maintaining tissue plasticity and the regenerative potential that characterizes IPF. CONCLUSION: The present work aims to elucidate-by applying the logic of simplicity-the bio-molecular mechanisms involved in MET activation in IPF. This clarification is crucial to accurately design MET blockade strategies within a fully personalized approach to IPF.

Overexpression of activin-A and -B in malignant mesothelioma - attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth.

Activin-A and activin-B, members of the TGF-ß superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth.

Quantification of cellular penetrative forces using lab-on-a-chip technology and finite element modeling.

Tip-growing cells have the unique property of invading living tissues and abiotic growth matrices. To do so, they exert significant penetrative forces. In plant and fungal cells, these forces are generated by the hydrostatic turgor pressure. Using the TipChip, a microfluidic lab-on-a-chip device developed for tip-growing cells, we tested the ability to exert penetrative forces generated in pollen tubes, the fastest-growing plant cells. The tubes were guided to grow through microscopic gaps made of elastic polydimethylsiloxane material. Based on the deformation of the gaps, the force exerted by the elongating tubes to permit passage was determined using finite element methods. The data revealed that increasing mechanical impedance was met by the pollen tubes through modulation of the cell wall compliance and, thus, a change in the force acting on the obstacle. Tubes that successfully passed a narrow gap frequently burst, raising questions about the sperm discharge mechanism in the flowering plants.

Phosphatidylinositol 4,5-bisphosphate is required for invasive growth in Saccharomyces cerevisiae.

Phosphatidylinositol phosphates are important regulators of processes such as the cytoskeleton organization, membrane trafficking and gene transcription, which are all crucial for polarized cell growth. In particular, phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has essential roles in polarized growth as well as in cellular responses to stress. In the yeast Saccharomyces cerevisiae, the sole phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) Mss4p is essential for generating plasma membrane PtdIns(4,5)P2. Here, we show that Mss4p is required for yeast invasive growth in low-nutrient conditions. We isolated specific mss4 mutants that were defective in cell elongation, induction of the Flo11p flocculin, adhesion and cell wall integrity. We show that mss4-f12 cells have reduced plasma membrane PtdIns(4,5)P2 levels as well as a defect in its polarized distribution, yet Mss4-f12p is catalytically active in vitro. In addition, the Mss4-f12 protein was defective in localizing to the plasma membrane. Furthermore, addition of cAMP, but not an activated MAPKKK allele, partially restored the invasive growth defect of mss4-f12 cells. Taken together, our results indicate that plasma membrane PtdIns(4,5)P2 is crucial for yeast invasive growth and suggest that this phospholipid functions upstream of the cAMP-dependent protein kinase A signaling pathway.

Effects of botulinum toxin type A on expression of genes in keloid fibroblasts.

BACKGROUND: Invasive growth of fibroblast cells, which is regulated by multiple biological factors, is the key event in the pathophysiology of keloid scars. Recent studies have suggested that botulinum toxin type A (BoNT-A) could inhibit invasive growth of keloids. However, the molecular mechanisms are unknown. OBJECTIVE: The authors explore the effect of BoNT-A on the expression of genes relevant to invasive growth in keloid fibroblasts. METHODS: With 112 genes that were relevant to invasive growth, the authors utilized microarray analysis to study messenger RNA expression profiles in keloid fibroblasts treated with BoNT-A. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to confirm the microarray results. RESULTS: Analyses from microarray and qRT-PCR revealed that the S100A4 gene was upregulated and that the TGF-ß1, VEGF, MMP-1, and PDGFA genes were downregulated in fibroblasts treated with BoNT-A. CONCLUSIONS: The BoNT-A altered expression levels of S100A4, TGF-ß1, VEGF, MMP-1, and PDGFA genes in keloid fibroblasts provide a useful clue for exploring the function of BoNT-A and finding a novel treatment for keloid scarring.

Septin-dependent invasive growth by the rice blast fungus Magnaporthe oryzae.

Septin GTPases are morphogenetic proteins that are widely conserved in eukaryotic organisms fulfilling diverse roles in cell division, differentiation and development. In the filamentous fungal pathogen Magnaporthe oryzae, the causal agent of the devastating blast diseases of rice and wheat, septins have been shown to be essential for plant infection. The blast fungus elaborates a specialised infection structure called an appressorium with which it mechanically ruptures the plant cuticle. Septin aggregation and generation of a hetero-oligomeric ring structure at the base of the infection cell is indispensable for plant infection. Furthermore, once the fungus enters host tissue it develops another infection structure, the transpressorium, enabling it to move between living host plant cells, which also requires septins for its function. Specific inhibition of septin aggregation-either genetically or with chemical inhibitors-prevents plant infection. Significantly, by screening for inhibitors of septin aggregation, broad spectrum anti-fungal compounds have been identified that prevent rice blast and a number of other cereal diseases in field trials. We review the recent advances in our understanding of septin biology and their potential as targets for crop disease control.

High intragenomic, intergenomic, and phenotypic diversity in pulcherrimin-producing Metschnikowia yeasts indicates a special mode of genome evolution.

In molecular systematics, the delimitation of yeast species is based on the notion that the barcode differences are smaller within species than between them. The most widely used barcodes are segments of the chromosomal repeats coding for ribosomal RNAs that are homogenised in yeasts. The analysis of these segments of the type strains of ten species recently merged in Metschnikowia pulcherrima and 37 new isolates demonstrated that this is not the case in this species. The intragenomic diversity significantly exceeded the threshold gaps used to differentiate related yeast species. Large segments of the D1/D2 domains were not diverse within the genomes and could therefore be used to determine the taxonomic affiliation of the isolates. The genome structures of the isolates were compared by RAPD and the RFLP of the mitochondrial DNA. Both patterns were highly heterogeneous. The sequence analysis of the PUL4 gene (a member of the PUL gene cluster involved in pulcherrimin production) revealed very high intragenomic differences, suggesting that the genomes may be chimerised. Three phenotypic traits related to the antimicrobial antagonism characteristic of the species were also highly diverse and prone to reversible segregation resembling epigenetic processes (silencing and reactivation of regulators) rather than mutations and back-mutations. These features make M. pulcherrima unique among yeasts and indicate that it evolves in a non-standard way.

Conserved signaling modules regulate filamentous growth in fungi: a model for eukaryotic cell differentiation.

Eukaryotic organisms are composed of different cell types with defined shapes and functions. Specific cell types are produced by the process of cell differentiation, which is regulated by signal transduction pathways. Signaling pathways regulate cell differentiation by sensing cues and controlling the expression of target genes whose products generate cell types with specific attributes. In studying how cells differentiate, fungi have proved valuable models because of their ease of genetic manipulation and striking cell morphologies. Many fungal species undergo filamentous growth-a specialized growth pattern where cells produce elongated tube-like projections. Filamentous growth promotes expansion into new environments, including invasion into plant and animal hosts by fungal pathogens. The same signaling pathways that regulate filamentous growth in fungi also control cell differentiation throughout eukaryotes and include highly conserved mitogen-activated protein kinase (MAPK) pathways, which is the focus of this review. In many fungal species, mucin-type sensors regulate MAPK pathways to control filamentous growth in response to diverse stimuli. Once activated, MAPK pathways reorganize cell polarity, induce changes in cell adhesion, and promote the secretion of degradative enzymes that mediate access to new environments. However, MAPK pathway regulation is complicated because related pathways can share components with each other yet induce unique responses (i.e. signal specificity). In addition, MAPK pathways function in highly integrated networks with other regulatory pathways (i.e. signal integration). Here, we discuss signal specificity and integration in several yeast models (mainly Saccharomyces cerevisiae and Candida albicans) by focusing on the filamentation MAPK pathway. Because of the strong evolutionary ties between species, a deeper understanding of the regulation of filamentous growth in established models and increasingly diverse fungal species can reveal fundamentally new mechanisms underlying eukaryotic cell differentiation.

The cellular mechanics of an invasive lifestyle.

Invasive behaviour is the hallmark of a variety of cell types of animal, plant, and fungal origin. Here we review the purpose and mechanism of invasive growth and migration. The focus is on the physical principles governing the process, the source of invasive force, and the cellular mechanism by which the cell penetrates the substrate. The current experimental methods for measuring invasive force and the modelling approaches for studying invasive behaviour are explained, and future experimental strategies are proposed.