Predicting the impacts of non-native species remains one of the greatest challenges to invasion ecologists. Because of their insularity, freshwater systems are particularly vulnerable to invasions, especially from non-native predators. The research in this thesis explores the role of abiotic and biotic factors in mediating the distribution and impact of Bythotrephes longimanus, a predatory cladoceran that has been introduced to freshwater systems in North America. Although the general impacts of this invasion have been documented, little is known about the factors that modulate them. Using a combination of field surveys and experiments, I tested several hypotheses concerning the influence of interactions with native species, as well as the role of heterogeneity in the light environment, in mediating the impact of Bythotrephes. Results demonstrated that biotic resistance by native macroinvertebrate predators does not play a limiting role in the establishment success of Bythotrephes. However, the within-lake distribution of Bythotrephes was influenced by these macroinvertebrates, suggesting that the native predator context matters when trying to understand the impacts of non-native predators. This was demonstrated with a mesocosm experiment in which the impact of Bythotrephes was constrained by the native Chaoborus larvae. In terms of the abiotic environment, in situ feeding experiments demonstrated that refuges from impact could exist for some prey taxa, as the outcome of predation by Bythotrephes was dependent on light availability and some prey taxa were more successful at evading predation under low light conditions. Finally, results show that adaptive behaviour by prey is also an important determinant of impact, as migrating Daphnia can escape predation effects by Bythotrephes. The combination of light-limited predation and a shallow distribution by Bythotrephes selects for prey that occupy relatively deeper positions during the day. As a whole, this research highlights the importance of complex interactions in mediating the impact of Bythotrephes and may help to explain some of the variation that has been documented among invaded lakes. A better understanding of these complex interactions can improve our ability to anticipate impacts as Bythotrephes continues to spread, as well as provide insight on some of the long-term effects following invasion. / Thesis (Ph.D, Biology) -- Queen's University, 2013-06-17 09:26:35.221

<p>Basement membrane (BM) is the thin, dense, highly cross-linked form of extracellular matrix that underlies all epithelia and endothelia, as well as surrounds muscle, nerve and fat. These sheet-like networks function as physiological barriers to maintain tissue homeostasis. During normal developmental processes and immune surveillance, cells invade through BM to establish tissues and fight infection. Similarly, metastatic cancer cells are thought to co-opt normal programs for BM transmigration as they spread from primary tumors and colonize distant tissues. The difficulty of visualizing cell-BM interactions during invasion in vivo has left the cellular and molecular mechanisms used to breach BM undefined. Specialized F-actin-rich matrix-degrading membrane protrusions, termed invadosomes, have been described in cultured invasive cell lines for more 30 years. Invadosomes are hypothesized to mediate BM penetration during cancer metastasis. Despite promising advances in intravital imaging technologies, however, invadosomes have yet to be observed in cells transmigrating BM in vivo, leaving their physiological relevance unclear. Anchor cell invasion in C. elegans is a simple in vivo model of cell invasion that allows for combined visual and genetic analysis of BM transmigration. In this dissertation I develop high-resolution time-lapse imaging approaches to understand the dynamic interactions that occur at the AC-BM interface during invasion. Through the course of this work we identify an integrin-based mechanism that polarizes the AC towards the BM. We further discover protrusive F-actin-based invadosome structures that mediate BM breach during anchor cell (AC) invasion. We find that in most cases only one or two invadosomes penetrate the BM and then transform into an invasive protrusion that guides the AC through a single BM gap. Using genetics and quantitative single-cell image analysis we characterize several molecular regulators of invadosome formation in vivo. Our findings establish an essential role for invadosomes during BM transmigration in vivo, and support the idea that these structures are a core, conserved element of a normal invasive cellular strategy activated during cancer metastasis.</p> / Dissertation

Seed dispersal by caching rodents is a context-dependent mutualism in many systems. Plants benefit when seed remaining in shallow caches germinates before being eaten, often gaining protection from beetles and a favorable microsite in the process. Caching in highly unfavorable microsites, conversely, could undermine the dispersal benefit for the plant. Plant invasions could disrupt dispersal benefits of seed caching by attracting rodents to the protection of a dense invasive canopy which inhibits the establishment of native seedlings beneath it. To determine whether rodents disproportionately cache seed under the dense canopy of an invasive grass in southeastern Arizona, we used nontoxic fluorescent powder and ultraviolet light to locate caches of seed offered to rodents in the field. We fitted a general habitat-use model, which showed that disproportionate use of plant cover by caching rodents (principally Chaetodipus spp.) increased with moonlight. Across all moon phases, when rodents cached under plants, they cached under the invasive grass disproportionately to its relative cover. A greenhouse experiment showed that proximity to the invasive grass reduced the growth and survival of seedlings of a common native tree (Parkinsonia microphylla) whose seeds are dispersed by caching rodents. Biased dispersal of native seed to the base of an invasive grass could magnify the competitive effect of this grass on native plants, further reducing their recruitment and magnifying the effect of the invasion.

De récentes études ont identifié la créativité tactique (CT) comme un élément essentiel de la performance en sport, plus particulièrement dans les sports d’équipe où il faut envahir le camp adverse pour marquer un point (Memmert, Baker & Bertsch, 2010 ; Altavilla & Raiola, 2015). En effet, la dynamique continue du jeu confronte l’athlète à de nouvelles situations pour lesquelles il n’a pas appris de séquences d’action prédéterminées. L’athlète créatif est donc celui qui est capable de générer des solutions originales, flexibles et variées dans des situations de jeu spécifiques (Memmert & Roth, 2007 ; Greco, Memmert & Morales, 2010). Cette étude qualitative a pour but d’explorer le phénomène de la créativité tactique telle qu’elle est perçue et vécue par des athlètes et des entraîneurs de niveau universitaire évoluant dans certains sports d’invasion. Des entrevues semi-structurées ont été menées avec les entraîneurs-chefs et leurs athlètes identifiés comme étant des joueurs créatifs. Les transcriptions ont été soumises à une analyse de contenu. Les résultats suggèrent que les athlètes créatifs partagent des caractéristiques communes, les plus importantes étant la vision du jeu, la non-conformité/nouveauté et la rapidité de la prise de décision. Dans une perspective développementale, la CT est liée à la diversification entre et dans les sports ainsi qu’un volume élevé d’expérience. La microstructure des activités d’entraînement contribue également au développement d’habiletés créatives, plus particulièrement les exercices centrés sur le jeu qui favorise la résolution de problèmes et la prise de décision. Contrairement aux études précédentes, nos résultats révèlent que le coaching soutenant l’autonomie et une relation positive entre l’athlète et l’entraîneur facilite le développement de la créativité ce qui nous permet de faire des liens avec la théorie de l’autodétermination. Enfin, la CT est associée à des conséquences tant au niveau social que de la performance. Bien qu’inattendu, la CT semble jouer un rôle fonctionnel dans l’utilisation de stratégies de coping adaptées. Les implications pratiques se définissent en deux axes. D’une part, fournir aux entraîneurs des lignes directrices pour créer un environnement idéal afin d’améliorer le développement de la CT. D’autre part, conscientiser les athlètes quant à l’importance de certains facteurs environnementaux et développementaux qui contribuent à maximiser leur potentiel créatif. / Tactical creativity (TC) has been identified as an essential component of exceptional performance in sport, more specifically in team sports where the athletes have to invade the opposition’s territory to score a goal (Altavilla et Raiola, 2015; Memmert, Baker et Bertsch, 2010). The creative athlete is one who can generate original, flexible and varying decisions in specific game situations (Greco, Memmert et Morales, 2010; Memmert et Roth, 2007). The purpose of this qualitative study was to explore in greater depth the phenomenon of tactical creativity as it is perceived and experienced by university-level athletes and coaches involved in certain invasion sports. Semi-structured interviews were conducted with head coaches of different teams and their athletes who were identified as being creative players. Transcripts were analyzed using content analysis. Results pointed to common attributes shared by creative players, the most important ones were game vision, non-conformity/novelty and quick decision-making. From a developmental perspective, TC was linked to diversification between and within sports as well as a high volume of experience. The microstructure of practice activities also contributed to the development of creative abilities, more specifically game-centered exercises that promote decision making and problem solving. Unlike previous studies, the present results revealed that autonomy-supportive coaching and a positive coach-athlete relationship facilitate the development of creativity allowing us to make links to the self-determination theory. Finally, TC was associated with social and performance related consequences. Interestingly, our results suggest a functional role for tactical creativity in the use of adaptive coping mechanisms. The practical implications of this study are twofold. First, the results of this study will provide coaches with specific guidelines in order to establish an ideal environment that enhances the development of TC. Second, the results will provide athletes with an awareness of the importance of certain developmental and environmental factors that contribute to maximizing their creative potential.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mediální obraz vstupu vojsk Varšavské smlouvy do Československa ve vybraných italských denících Media portrayal of Warsaw pact invasion to Czechoslovakia in selected Italian newspapers Bc. Sabina Růžičková Abstract The diploma work "Media portrayal of Warsaw pact invasion to Czechoslovakia in selected Italian newspapers" brings closer look at this historical phenomena from the view of several Italian newspapers. The task was to analyze journals published on the Apennine Peninsula and their reporting about this invasion regarding their political profile. The examined units were the form, the content and size of reports. In the beginning of my thesis, I was trying to provide a closer look at the situation in Czechoslovakia in 1968, the process of becoming more liberal and free, which was violently interrupted in August 1968 by the Warsaw troops. In the end of my diploma, I used a comparative historical analysis to see how the particular Italian media informed its readers about the situation and how much they different in the point of view at the situation

This Master Thesis is called Media Image of the Bay of Pigs Invasion of Cuba in the Czechoslovakia Contemporary Press. Its aim is to show overall picture of how was the Invasion characterized by four contemporary daily newspapers - Rudé právo, Lidová demokracie, Mladá fronta a Obrana lidu. The first part of this thesis describes the historical background of the Bay of Pigs Invasion and the Invasion itself, relationship between Cuba and Czechoslovakia, what was the media situation, censorship, propaganda and short introduction of the newspapers. Next part analyses the contemporary newspaper articles, which puts together media image of the Invasion. During the Cold War, the Invasion of the Bay of Pigs was the first serious conflict between Cuba and the USA.

Neospora caninum (Apicomplexa) é o agente causador da neosporose, descrita como a principal causa de aborto parasitário em gado bovino .Parasitos desse filo interagem e invadem as células hospedeiras através da secreção coordenada de proteínas do complexo apical, formado por diversas organelas, dentre elas as roptrias (ROPs), que desempenham papel fundamental no processo de infecção, associado à formação do vacúolo parasitóforo (PV), sobrevivência no ambiente intracelular e virulência do parasito. Essas proteínas podem ser caracterizadas em: proteínas de roptrias de pescoço (RONs), e proteínas de roptrias (ROPs). Além disso, algumas ROPs podem se diferenciar e, dessa maneira, constituem uma grande família de quinases e pseudo-quinases, denominada família de roptrias quinase (ROPKs). O objetivo deste estudo foi caracterizar as proteínas de roptrias NcROP15B (NcLIV_011700) e NcROP55 (NcLIV_031550) de N. caninum. As sequências de NcROP15B e NcROP55 foram alinhadas com homólogos de alguns microrganismos, incluindo apicomplexas, ao BLAST. NcROP15B apresentou identidade de 19% com as sequencias de ROP15 de T. gondii e Hammondia hammondi. NcROP55 mostrou identidade de 14% com a ROP37 de T. gondii e com ROP28 de Hammondia hammondi, e 15% com a ROP28 de Neospora caninum. Foram detectados domínios pertencentes à família de proteínas quinase para NcROP15B e NcROP55, e peptídeo sinal apenas para NcROP15B. Os primers foram delineados para amplificar regiões de cDNA de ambos os genes com diferentes tamanhos, denominados NcROP15B maior, NcROP15B menor, NcROP55 maior e NcROP55 menor. Os insertos foram subclonados (pGEM) e posteriormente ligados em plasmídeo de expressão pET28 em E. coli BL21(DE3) e a expressão recombinante induzida por IPTG. As formas recombinantes foram expressas com 30 kDa e 16 kDa (NcROP15B fragmento Maior e Menor, respectivamente) e NcROP55 Maior e Menor gerou um peso molecular de 19.9 kDa e 15 kDa, respectivamente. Após purificação, NcROP15B e NcROP55 foram utilizadas para obtenção de soros policlonais. Anti-ROP15B e anti-ROP55 reagiram com extrato de N. caninum em Western Blot 1D, tendo NcROP15B sido detectada com 35 kDa, próximo ao predito (32 kDa) e NcROP55 com aproximadamente 35 KDa, porém abaixo do predito (47.9 kDa). Na imunofluorescência confocal, NcROP-15B e NcROP55 exibiram padrão de localização na região perinuclear de taquizoítos de N. caninum. Os anticorpos anti-NcROP15B e anti-NcROP55 apresentaram, individualmente, capacidade limitada para inibir o processo de adesão/invasão de N. caninum, sendo 16% e 6,43% respectivamente. Quando os soros anti-NcROP15B e anti-NcROP55 foram associados, a a inibição da invasão aumentou para 62%. As proteínas NcROP-15B e NcROP55 podem representar quinases importantes no metabolismo de N. caninum, e podem estar relacionadas ao processo de invasão e proliferação do parasito. Dessa maneira, são possíveis alvos para se considerar no estudo de medidas preventivas, sendo necessários mais estudos para avaliar suas funções na sobrevivência intracelular e virulência de N. caninum. / Neospora caninum (Apicomplexa) is the causative agent of neosporosis, described as the main responsible of parasitic abortion in cattle. Parasites of this phylum interact and invade the host cells through a coordinated secretion of proteins of the apical complex, formed by organelles like rhoptries, which play a key role in the infection process, associated to the formation of the parasitophorous vacuole (PV), intracellular survival and parasite virulence. These proteins can be characterized in: neck rhoptry proteins (RONs), and rhoptry proteins (ROPs). Some ROPs can differentiate and thus constitute a large family of kinases and pseudo-kinases, called the kinase rhoptry family (ROPKs). The aim of this study was to characterize N. caninum NcROP15B (NcLIV_011700) and NcROP55 (NcLIV_031550) rhoptry proteins. The amino acid sequences of NcROP15B and NcROP55 were aligned with homologous proteins from some microorganisms, including apicomplexan on BLAST. NcROP15B showed a 19% identity with the ROP15 of T. gondii and Hammondia hammondi. NcROP55 had 14% of identity with ROP37 of T. gondii and with ROP28 of Hammondia hammondi, and 15% with ROP28 of Neospora caninum. Domains were detected belonging to the protein kinase family for NcROP15B and NcROP55, and signal peptide only for NcROP15B. Primers were designed to amplify cDNA regions of both genes, opting for fragments of different sizes, names as NcROP15B major, NcROP15B minor, NcROP55 major and NcROP55 minor. The inserts were subcloned (pGEM) and then ligated into pET28 expression plasmid in E. coli BL21 (DE3) and IPTG-induced recombinant expression. The recombinant forms were expressed with 30 kDa and 16 kDa (NcROP15B Major and Minor, respectively) and Major and Minor NcROP55 had molecular weights of 19.9 kDa and 15 kDa, respectively. After purification, NcROP15B and NcROP55 were used to obtain polyclonal serum. Anti-ROP15B and anti-ROP55 reacted with N. caninum extract in Western Blot 1D, with NcROP15B being detected at 35 kDa, near predicted (32 kDa) and NcROP55 at approximately 35 KDa, but below the predicted (47.9 kDa). At confocal immunofluorescence, NcROP-15B and NcROP55 exhibited a localization pattern at the perinuclear region of N. caninum tachyzoites. Anti-NcROP15B and anti-NcROP55 antibodies had, individually, limited ability to inhibit the N. caninum adhesion/invasion process (16 and 6,43%, respectively). When associated, anti-NcROP15B and anti-NcROP55 sera inhibition of invasion increased to 62%. NcROP-15B and NcROP55 proteins might represent important kinases in the metabolism of N. caninum with a possible role in the parasite invasion and proliferation process. Thus, they represent possible targets for preventive measures, but further studies are necessary to evaluate their functions in intracellular survival and virulence of N. caninum.

O câncer colorretal (CCR) é o terceiro tipo de câncer mais comum no mundo. Apesar dos avanços nos tratamentos convencionais, aproximadamente dois terços dos pacientes com CCR são submetidos à cirurgia potencialmente curativa. Entretanto, grande parte desses pacientes evolui mal, apresentando recidivas e/ou metástases. A busca de novos alvos moleculares para a terapia do CCR revelou a proteína celular Prion (PrPC) como um possível candidato. Trabalhos recentes sugerem participação direta ou indireta de PrPC no crescimento de tumores, na formação de metástases, na composição de complexos multiproteicos e na indução de vias de sinalização envolvidas em diversos processos biológicos, como proliferação. Além disso, PrPC foi descrito como um importante modulador do crescimento de tumor colorretal. Resultados prévios mostraram que a interação da proteína PrPC com a proteína HSP70/HSP90 Organizing Protein (HOP) induz proliferação em glioblastomas. HOP é uma proteína predominantemente citoplasmática, podendo também ser secretada associada às vesículas extracelulares. Assim, o presente estudo objetivou avaliar o papel do complexo PrPC-HOP e das vesículas extracelulares no desenvolvimento e progressão dos tumores colorretais. Os nossos resultados mostram que HOP induziu migração e invasão em linhagens de CCR de maneira dependente de PrPC, uma vez que o uso do peptídeo sem atividade que compete pelo sítio ligação de HOP a PrPC inibiu estes processos. Além disso, nossos dados apontaram que o aumento de migração e invasão das células de CCR induzida pela interação PrPC-HOP é mediada pela ativação da via ERK1/2. Os achados in vitro estimularam a avaliação do perfil de expressão de PrPC e HOP por imuno-histoquímica em tecidos de pacientes com diferentes tipos de tumores colorretais. Nossos resultados sugeriram que essas proteínas são importantes no início do desenvolvimento tumoral e na transição de adenomas para adenocarcinomas, não havendo correlação entre a presença de HOP e/ou PrPC com metástase, linfonodos acometidos, estadiamento, sobrevida ou região tumoral versus tecido normal. Em relação ao papel das vesículas extracelulares na progressão dos tumores colorretais, nossos resultados mostraram que linhagens celulares que apresentam padrões parecidos de agressividade tumoral podem ter perfis de secreção de proteínas e vesículas extracelulares bastante diferentes, induzindo, portanto, processos biológicos com intensidades distintas. O meio condicionado e as vesículas extracelulares da linhagem WiDr apresentaram maior potencial de indução de migração quando comparado com a linhagem HCT8. Além disso, a modulação negativa da proteína VPS4, uma das responsáveis pela formação dos corpos multivesiculares, mostrou-se uma abordagem interessante no estudo da secreção de vesículas por células de CCR, uma vez que o dominante negativo de VPS4 promoveu diminuição do cargo proteico e da secreção de vesículas extracelulares, redução da proliferação celular e do efeito indutor do processo de migração na linhagem WiDr. Assim, em conjunto, o presente trabalho indicou que o complexo PrPC-HOP pode ser um bom alvo terapêutico nos processos de migração e invasão em CCR. Ainda, essas proteínas se mostraram importantes nos estágios iniciais da formação dos tumores. A modulação da secreção de vesículas extracelulares pode contribuir para retardar a progressão dos tumores colorretais. / Colorectal cancer (CRC) is the third most common type of cancer in the world. Despite improvements in conventional treatments, approximately two-thirds of CRC patients undergo potentially curative surgery. However, most of these patients evolve poorly, showing recurrence and/or metastasis. Search of new molecular targets for CRC therapy revealed the cellular protein Prion (PrPC) as a putative candidate. Recent studies have shown that PrPC exhibit direct or indirect participation in tumor growth, formation of metastasis, composition of multiprotein complexes and induction of signaling pathways involved in many biological processes such as proliferation. Moreover, PrPC has been described as an important modulator of colorectal tumor growth. Previous findings showed that the interaction between PrPC and its ligand HSP70/90 heat shock organizing protein (HOP) induces gliobastoma proliferation. It is well known that HOP localizes mainly in the cytoplasm but HOP is also secreted associated with extracellular vesicles. In this way, the present study sought to evaluate the role of PrPC-HOP complex and extracellular vesicles in the development and progression of CRC. We demonstrate that HOP induces the migration and invasion of CRC cell lines in a PrPC-dependent manner because the use of HOP peptide, which is able to bind to PrPC, blocking PrPC-HOP complex formation, inhibited the migration and invasion processes. In addition, our data showed that the enhancement of migration and invasion induced by PrPC-HOP interaction is mediated by ERK1/2 pathway activation. These in vitro results lead us to evaluate the PrPC and HOP expression by immunohistochemistry in tissues from patients with different tumor types. Our data showed that these proteins could be important for the initial steps of tumor development, represented by the transition from adenoma to adenocarcinoma. No correlation was found among HOP and/or PrPC expression and metastasis, lymph node involvement, staging, survival or tumor area versus normal tissue. Regarding the role of extracellular vesicles in the progression of colorectal tumors, our results showed that cell lines exhibiting similar aggressive tumor behavior can have a different protein secretion pattern and a distinct profile of extracellular vesicles release, which could induce biological process with different intensities. The conditioned medium and the extracellular vesicles derived from WiDr cell line showed a higher potential to induce migration than HCT8 cell line. Moreover, the negative modulation of VPS4, one of the proteins responsible for multivesicular body formation, showed to be an interesting approach in the study of extracellular vesicles secretion secreted by CRC cells; the negative dominant of VPS4 promoted in the WiDr cell line a reduction in the protein cargo and secretion of the extracellular vesicles, a decrease of cell proliferation and induction of migration process. Therefore, taken together, our data highlights that PrPC-HOP complex can be considered a new therapeutic target in migration and invasion processes of CRC. Moreover, these proteins appeared to be important at onset of tumor formation. The modulation of extracellular vesicles secretion may contribute for delaying the progression of colorectal tumors.

Os pacientes com melanomas, em geral, apresentam extrema quimiorresistência e prognóstico ruim, com taxa de sobrevida de aproximadamente seis meses; portanto, novas estratégias terapêuticas são necessárias. As células deste tipo de tumor acumulam alterações na expressão gênica que contribuem para a proliferação descontrolada, evasão de senescência e inibição de morte celular em múltiplas rotas intracelulares. No Capítulo 1, foi explorado o controle epigenético do supressor tumoral RECK. Esse gene é largamente expresso em tecidos normais, com correlação de sua expressão com melhor prognóstico. Em tumores, RECK é inibido, incluindo em melanoma. Neste estudo, sua inibição por hipermetilação do promotor e remodelamento da cromatina por HDACs não foi o único fator inibitório nas linhagens de melanoma analisadas. Mesmo após a utilização a remoção de marcas epigenéticas associadas ao silenciamento gênico, a expressão proteica não pôde ser recuperada nas linhagens utilizadas neste trabalho. No Capítulo 2, isolou-se subpopulações clonais ao acaso a fim de modelar a heterogeneidade tumoral intrínseca. Neste modelo experimental, caracterizamos a presença de dois perfis tumorais subclonais: uma mais proliferativa, invasiva e sensível a vemurafenibe; e outra menos proliferativa, mais resistente e com maior expressão de RECK e fatores ligados a EMT. Nossos resultados, em conjunto, mostraram que as linhagens celulares parentais utilizadas apresentam diferenças entre si quanto à viabilidade celular, indução de apoptose e fosforilação de ERK após o tratamento com vemurafenibe. Segundo o nosso modelo, a resistência intrínseca ao vemurafenibe está presente e reflete a heterogeneidade do tumor inicial. Com estes resultados, pretendemos contribuir para o conhecimento sobre a composição clonal presente na heterogeneidade tumoral, além de contribuir para a função de RECK na biologia do melanoma. / Patients with melanoma often present extreme chemoresistance and poor prognosis, with survival rates of approximately six months; therefore, new therapeutic strategies are necessary. Melanoma cells accumulate genotypic changes that contribute to uncontrolled proliferation, evasion of senescence and cell death inhibition in multiple cellular pathways. In Chapter 1, we have explored the epigenetic control of the tumor suppressor RECK. This gene is widely expressed in normal tissues, with correlation of its expression with better prognosis. In tumors, RECK is inhibited, including melanoma. Here, RECK inhibition by promoter hypermethylation and chromatin remodeling by HDACs was not the only inhibiting factor in the melanoma cell lines analyzed. Even after removing the epigenetic marks associated to gene expression silencing, the protein expression could not be recovered in the cell lines used in this study. In Chapter 2, it has been isolated several tumor clonal subpopulations in order to modulate the intrinsic tumor heterogeneity. In this experimental model, we have characterized the presence of two tumor subclonal profiles: a more proliferative, invasive and sensitive to Vemurafenib; and other less proliferative, less sensitive to Vemurafenib and presenting more expression of RECK and factors associated to EMT. Our results together have showed the parental cell lines used here differed from each other in terms of cell viability, induction of apoptosis, and ERK phosphorylation after treatment with Vemurafenib. According to our model, the intrinsic resistance to Vemurafenib is present and reflects the heterogeneity of the initial tumor. With these results, we intend to contribute to the knowledge of the tumor clonal subpopulations composition in tumor heterogeneity, and contributes to the RECK function in melanoma biology.