ß-Catenin: oncogenic role and therapeutic target in cervical cancer

Cervical cancer is a common and fatal malignancy of the female reproductive system. Human papillomavirus (HPV) is the primary causal agent for cervical cancer, but HPV infection alone is insufficient to cause the disease. Actually, most HPV infections are sub-clinical and cleared spontaneously by the host immune system; very few persist and eventually develop into cervical cancer. Therefore, other host or environmental alterations could also contribute to the malignant phenotype. One of the candidate co-factors is the ß-catenin protein, a pivotal component of the Wnt/ß-catenin signaling pathway. ß-Catenin mainly implicates two major cellular activities: cell-cell adhesion and signal transduction. Recent studies have indicated that an imbalance in the structural and signaling properties of ß-catenin leads to various cancers, such as cervical cancer. In this review, we will systematically summarize the role of ß-catenin in cervical cancer and provide new insights into therapeutic strategies.

Effect of PCB118 on cell adhesion of human hepatocellular carcinoma cells BEL-7402 / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects and mechanism of PCB118 on cell-matrix and cel-cel adhesion in human hepatocel ular carcinoma cel s. METHODS Human hepatocel ular carcinoma cel s BEL-7402 were treated with PCB118 0.1,1.0 and 10.0 nmol · L-1 for 4 or 6 d,respectively. Then the cell-matrix adhesion assay and cell aggregation experiments were conducted to study the effect of PCB118 on cell-matrix adhesion and cell-cell adhesion in BEL-7402 cells. Quantitative real-time PCR and Western blotting methods were employed to assess the expression of key cytokines CD29,N-cadherin and E-cadherin. RESULTS The results showed that the cell-matrix adhesion ability of human hepato?cellular carcinoma cells BEL-7402 were significantly increased(P<0.05)after treatment with PCB118 0.1,1.0 and 10.0 nmol·L-1 for 6 d,whereas the cell-cell adhesion ability was significantly reduced(P<0.05). Exposure to PCB118(0.1,1.0 and 10.0 nmol·L-1)for 6 d induced significant upregulation of the mRNA expression levels of CD29 and N-cadherin along with the downregulation of E-cadherin(P<0.05). Western blotting analysis revealed that PCB118 exposure significantly increased protein expressions of CD29 and N-cadherin but reduced E-cadherin protein level(P<0.01). CONCLUSION PCB118 exposure affects the expression of CD29,N-cadherin and E-cadherin, which may be involved in PCB118-induced alteration of cell adhesion of hepatocellular carcinoma cell line BEL-7402.

Mecanismos celulares e moleculares modulados por PGE2 e TGFβ durante a progressão do câncer colorretal

Um dos primeiros eventos associados à progressão do câncer colorretal (CCR) é a perda dos contatos célula-célula, seguido da aquisição de um fenótipo indiferenciado e aumento na motilidade celular. Estes eventos estão associados com um processo conhecido como transição epitélio-mesenquimal (TEM), na qual as células adquirem capacidade para invadir tecidos vizinhos. A biogênese deste tipo de câncer envolve uma série de fatores predisponentes dentre os quais está o processo infamatório, onde a prostaglandina E2 (PGE2) e o fator transformador β de crescimento (TGFβ) cumprem importante função. Vários estudos têm mostrado que a PGE2 induz proliferação, migração e invasão celular. Já o TGFβ, apesar de ter uma função dual como promotor ou supressor da tumorigênese, é conhecido também por promover TEM em diferentes tipos de câncer. No entanto, a associação entre as vias de sinalização celular ativada por estes agentes na indução da perda da adesão célula-célula e da TEM em CCR não é conhecida. No presente estudo, usando linhagens celulares de CCR, analisamos a associação entre a PGE2 e o TGFβ sobre as alterações no fenótipo celular e eventos relacionados com a TEM. Na primeira etapa do estudo, usando células Caco-2, mostramos que o tratamento com PGE2 promoveu alterações na localização e função de proteínas do complexo juncional apical (CJA) concomitantemente com a perda da funcionalidade da barreira paracelular. Mostramos também que a via de sinalização responsável nesse evento foi a PKC através de um mecanismo envolvendo os receptores prostanóides EP1 e EP2 e a proteína claudina-1 na modulação do CJA. Na segunda etapa do estudo, analisamos eventos relacionados com a TEM usando linhagens celulares de CCR que diferem no fenótipo e no grau de invasão mediante tratamentos com PGE2 e TGFβ...

The lost of cell-cell adhesion followed by increased motility and acquisition of an undifferentiated phenotype are initial events associated with colorectal cancer (CCR) progression. These events are associated with a process known as epithelial-mesenchymal transition (TEM) in which cells acquire the ability to invade neighboring tissues. The biogenesis of this type of cancer predisposes a series of conditions for which the inflammatory process, known as an important inductor of prostaglandin E2 (PGE2) and tumor growth factor β (TGFβ), plays an important function. Various studies have shown that PGE2 is able to induce proliferation, migration and invasion. TGFβ plays a dual function either as promoter or tumor suppressor and is also a TEM inductor in different types of cancer. However, a crosslink between the cell signaling pathways activated by these agents in relation to lost of cell-cell adhesion and TEM development in CCR is unknown. In the present study, using CCR cell lines, we analyze the association between PGE2 and TGFβ...