1,720,977 research outputs found
Connecting epithelial polarity, proliferation and cancer in Drosophila: the many faces of lgl loss of function
No full textLoss of cell polarity is a prominent feature of epithelial cancers. Several tumour-suppressor genes are indeed involved in establishing and maintaining a correct apical-basal polarity suggesting
that a link exists between disruption of epithelial polarity and the control of cell proliferation. Nevertheless, the molecular basis of this link is only beginning to be unveiled. In Drosophila, the tumour suppressor gene lethal giant larvae (lgl) is widely used as a genetic tool in cancer modelling:
its loss of function causes neoplastic growth of the imaginal tissues, larval epithelial organs from which adult structures originate. These mutant epithelia are characterised by loss of cell polarity and tissue architecture as well as hyperproliferation. We observed that in a clonal context, the ability of lgl mutant cells to express their neoplastic potential correlates with the levels of the oncoprotein Myc, a master regulator of cell growth and proliferation. Malignant, polarity-deficient mutant cells upregulate Myc and are able to overcome the tumour-suppressive defences imposed by the surrounding wild-type tissue. How does the loss of lgl function induce an increase in Myc levels? The answer to this question came from the finding that Lgl is an upstream regulator of the Hippo pathway, a highly conserved signalling network that controls proliferation of epithelial cells and organ size. The core of this pathway responds to several upstream regulators and converges on the inhibition of a transcriptional co-factor, Yorkie, which, as we and others have shown, is a direct regulator of the myc promoter. In this review we discuss the key findings that contributed to the identification of this regulatory network that links cell polarity to cell proliferation control
Drosophila Lethal Giant Larvae Neoplastic Mutant as a Genetic Tool for Cancer Modelling
No full textDrosophila lethal giant larvae (lgl) is a tumour suppressor gene whose function in establishing apical-basal cell polarity as well as in exerting proliferation control in epithelial
tissues is conserved between flies and mammals. Individuals bearing lgl null mutations show a gradual loss of tissue architecture and an extended larval life in which cell proliferation never ceases and no differentiation occurs, resulting in prepupal lethality. When tissues from
those individuals are transplanted into adult normal recipients, a subset of cells, possibly the cancer stem cells, are able to proliferate and migrate to distant sites forming metastases which eventually kill the host. This phenotype closely resembles that of mammalian epithelial cancers, in which loss of cell polarity is one of the hallmarks of a malignant, metastatic behaviour associated with poor prognosis. Lgl protein shares with its human counterpart
Human giant larvae-1 (Hugl-1) significant stretches of sequence similarity that we demonstrated to translate into a complete functional conservation, pointing out a role in cell
proliferation control and tumourigenesis also for the human homologue. The functional conservation and the power of fly genetics, that allows the researcher to manipulate the fly
genome at a level of precision that exceeds that of any other multicellular genetic system, make this Drosophila mutant a very suitable model in which to investigate the mechanisms
underlying epithelial tumour formation, progression and metastatisation. In this review, we will summarise the results obtained in the last years using this model for the study of cancer biology. Moreover, we will discuss how recent advances in developmental genetics techniques have succeeded in enhancing the similarities between fly and human tumourigenesis, giving Drosophila a pivotal role in the study of such a complex genetic disease
Growth and Tracheogenesis are Separable Traits in Drosophila Cancers
No full textDrosophila clonal cancer models provide an excellent contribution to the study of the molecular basis of tumourigenesis. A number of human cancer hallmarks are indeed functionally conserved; among them, overgrowth and vessel remodelling are particularly relevant to primary mass formation and cell dissemination throughout the organism.
We have previously identified MYC as a Hippo downstream target in Drosophila and demonstrated that cells with defects in polarity genes require MYC expression to overwhelm wild-type neighbours and develop into malignant masses. Recent data from our lab also showed that neo-tracheogenesis does occur in Drosophila cancers, and it is either functionally or molecularly analogous to mammalian tumour neo-angiogenesis.
Here I extended on previous work showing that, in Drosophila epithelial tumours, mass expansion and tracheogenesis are separable traits, dependent on MYC and FOS activity respectively. These two transcription factors are found at the intersection of the Hippo, JNK and Ras/MAPK signalling cascades, which are recognised as central actors in cancer progression
Tumour growth and tracheogenesis are separable cancer hallmarks in Drosophila
No full textClonal analysis is common practice in Drosophila. In particular, induction of cell clusters carrying both loss-of-function alleles of neoplastic tumour suppressors and activated forms of oncogenes has successfully been exploited to study cooperative tumourigenesis in different organs. This strategy has allowed to collect a number of morphological and molecular details on the phenotypic traits associated with cancer evolution. We previously identified Myc as a target of the Hippo pathway in Drosophila, and found out that its expression is sufficient to rescue the growth deficit of cells mutant for polarity genes, releasing their malignant potential. We also previously characterised cancer-associated tracheogenesis, a process analogue to mammalian neo-angiogenesis, as an intrinsic trait of Drosophila epithelial tumours. Here we expand on previous work, showing that tumour growth and tracheogenesis are separable traits in Drosophila epithelia. While in situ cancer expansion is mainly supported by Myc, this is not the case for migration and tracheogenesis, which mostly depend on Fos activity. These proteins are strategically found at the crossroads of the Hippo, JNK and Ras/MAPK pathways, which current literature recognises as key players in cancer progression
Cancer cells contribute to distinct malignant traits depending on their MYC and pJNK relative levels
No full textClonal analysis is common practice in Drosophila. In particular, induction of cell clusters carrying either loss-of-function alleles of neoplastic tumour suppressors or activated forms of oncogenes has successfully been exploited to study cooperative tumourigenesis in different organs. This strategy has allowed collecting a number of morphological and molecular details on the phenotypic traits associated with cancer progression. We previously identified MYC as a target of the Hippo pathway in Drosophila, and showed its expression is sufficient as to rescue the growth deficit of cells mutant for polarity genes, releasing their malignant nature. Here we expand on previous work, showing that cell growth and cell migration are separable traits in Drosophila epithelial cancers. While in situ cancer expansion is supported by MYC, migration depends on the AP-1 protein Fos. These proteins are strategically found at the crossroads of the Hippo, JNK and Ras/MAPK pathways, acknowledged by current literature as central players in cancer progression. Moreover, we show that growth and migration are mutually exclusive behaviours, with cells displaying different MYC and pJNK levels playing distinct roles in cancer evolution
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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