Assuntos
Colonoscopia , Hemorragia Gastrointestinal , Humanos , Hemorragia Gastrointestinal/etiologia , Recidiva , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Masculino , Amiloidose/complicações , Amiloidose/diagnóstico , Pessoa de Meia-Idade , Idoso , FemininoRESUMO
Colorectal cancer (CRC) is the third most common malignant tumor in humans. Chemotherapy is used for the treatment of CRC. However, the effect of chemotherapy remains unsatisfactory due to drug resistance. Growing evidence has shown that the presence of highly metastatic tumor stem cells, regulation of noncoding RNAs and the tumor microenvironment contributes to drug resistance mechanisms in CRC. Wnt/ßcatenin signaling mediates the chemoresistance of CRC in these three aspects. Therefore, the present study analyzed the abundant evidence of the contribution of Wnt/ßcatenin signaling to the development of drug resistance in CRC and discussed its possible role in improving the chemosensitivity of CRC, which may provide guidelines for its clinical treatment.
Assuntos
Neoplasias Colorretais , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas , Via de Sinalização Wnt , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genéticaRESUMO
The engulfment and cell motility (ELMOs) family of proteins plays a crucial role in tumor cell migration and invasion. However, the function of ELMO3 is poorly defined. To elucidate its role in the development and progression of colorectal cancer (CRC), we examined the expression of ELMO3 in 45 cases of paired CRC tumor tissues and adjacent normal tissues. Furthermore, we assessed the effect of the knockdown of ELMO3 on cell proliferation, cell cycle, migration, invasion and F-actin polymerization in HCT116 cells. The result shows that the expression of ELMO3 in CRC tissues was significantly increased in comparison to the adjacent normal colorectal tissues. Moreover, this overexpression was associated with tumor size (p = 0.007), tumor differentiation (p = 0.001), depth of invasion (p = 0.009), lymph node metastasis (p = 0.003), distant metastasis (p = 0.013) and tumor, node, metastasis (TNM)-based classification (p = 0.000). In in vitro experiments, the silencing of ELMO3 inhibited cell proliferation, invasion, metastasis, and F-actin polymerization, and induced Gap 1 (G1) phase cell cycle arrest. Our study demonstrates that ELMO3 is involved in the processes of growth, invasion and metastasis of CRC, and could be used a potential molecular diagnostic tool or therapy target of CRC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Proteínas do Citoesqueleto/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Actinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
PURPOSE: The aim of this study was to investigate the role of Li-cadherin in invasion and metastasis in LoVo cells. METHODS: We applied RNA interference mediated downregulation of Li-cadherin expression in LoVo cells. Li-cadherin expression in LoVo cells was examined by semiquantitative polymerase chain reaction, immunofluorescence, western blot, and immunoprecipitation, respectively. Effect of suppression of Li-cadherin expression on cell migration, invasion, and adhesion was detected by wound healing assay, migration assay, invasion assay, and adhesion assay. Expression and activity of MMP-2 and MMP-9 were analyzed by gelatin zymography. RESULTS: Cell migration, invasion, and adhesion were increased concomitantly with the reduction in Li-cadherin protein expression. Furthermore, downregulation of Li-cadherin expression induced secretion of proMMP-9, active MMP-9 and active MMP-2. CONCLUSIONS: This study suggests that silencing Li-cadherin has positive actions in the processes of LoVo cells invasion and metastasis, and the interactions among MMP-2, MMP-9, and Li-cadherin participate in the multiple steps of invasion and metastasis in LoVo colorectal cancer cells.
Assuntos
Caderinas/genética , Técnicas de Silenciamento de Genes , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Sequência de Bases , Adesão Celular , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Primers do DNA , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Plasmídeos/genética , Reação em Cadeia da Polimerase , RNA Neoplásico/genética , Transfecção , CicatrizaçãoRESUMO
BACKGROUND AND AIMS: Recent studies revealed that Musashi-1and beta1-integrin were putative stem cell genes. Overexpressions of Musashi-1 and beta1-integrin have been reported in some tumor tissues and cell lines. This study was to detect expressions of the two genes in colorectal adenomas and carcinomas and to analyze the correlation between Musashi-1 and beta1-integrin. METHODS: Musashi-1 and beta1-integrin immunoreactivity was studied immunohistochemically in tissue microarray-based samples containing 69 colorectal adenocarcinomas, eight normal mucosa, and eight adenomas, and their messenger RNA (mRNA) expression level was detected by RT-PCR in resected specimens including the three types of tissue. RESULTS: A percentage of 66.7% (46/69) and 59.2% (41/69) of colorectal adenocarcinomas were immunoreactive with Musashi-1 and beta1-integrin, respectively. The expressions of Musashi-1 and beta1-integrin protein were significantly higher in tissue samples of stage III than those of stage I-II (P = 0.0252; P = 0.0018, respectively). beta1-integrin expression was higher in group of adenocarcinomas than that of adenomas (P = 0.0276). Musashi-1 expression was closely correlated with beta1-integrin (rs = 0.631, P = 0.0001). Significant differences of Musashi-1 and beta1-integrin mRNA expression levels were found between the normal colorectal mucosa, adenoma, and adenocarcinoma tissues (P = 0.01; P = 0.03, respectively). CONCLUSIONS: Musashi-1 and beta1-integrin may be involved in human colorectal tumor carcinogenesis and progression. Our observations also indicate the need for further investigations to test in vivo whether cells with these markers have stem cell properties.
Assuntos
Adenocarcinoma/genética , Adenoma/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Integrina beta1/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Células-Tronco/metabolismo , Adenocarcinoma/patologia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Integrina beta1/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND AND AIMS: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is the main active subunit of HIF-1 that promoted tumor cells survival and critical steps in tumor progression and aggressiveness. The authors aimed to investigate the role of HIF-1 alpha and Survivin in colorectal cancer (CRC) progression. MATERIALS AND METHODS: Plasmid expressing small interfering RNA (siRNA) against HIF-1 alpha was constructed and transfected into LS174T cells with Lipofectamine. The LS174T cells were incubated for 24 h under hypoxic condition. The inhibitory effects of siRNA on HIF-1 alpha gene was determined by semiquantitative reverse transcriptase polymerase chain reaction and Western blot. Expression of HIF-1 alpha and Survivin was investigated by immunohistochemistry in colorectal adenocarcinomas tissue microarrays. RESULTS: HIF-1 alpha and Survivin expressions were markedly downregulated after the siRNA expression vector against HIF-1 alpha was transfected into the LS174T cells. Of the eight adenoma lesions, one case (12.25%) and four cases (50%) were positive for HIF-1 alpha and Survivin, respectively. Of the 69 cases of CRCs, 46 cases (66.7%) and 39 cases (56.5%) were positive for HIF-1 alpha and Survivin, respectively. The positive rate of HIF-1 alpha protein in CRCs was significantly higher than that in colorectal adenoma lesions (P < 0.05). HIF-1 alpha protein expression was significantly higher in patients with stage III than in patients with stage I-II CRCs (P < 0.01). In addition, overexpression of HIF-1 alpha in higher stages of CRCs was found to correlate positively with Survivin levels (P < 0.001). CONCLUSIONS: Our data demonstrate that HIF-1 alpha and Survivin are mostly expressed in invasive CRCs. Inhibition of HIF-1 alpha may lead to exploration of its potential as a diagnostic tool and possibly a target for gene therapy for colorectal carcinoma.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Western Blotting , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas de Neoplasias/biossíntese , Estadiamento de Neoplasias , RNA Neoplásico/biossíntese , RNA Interferente Pequeno/biossíntese , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SurvivinaRESUMO
The aims of this study were to examine the expressions of Li-cadherin and Galectin-3 in gastric cancer, and the correlation between Li-cadherin and Galectin-3 in gastric cancer was also analyzed. The present study investigated the expression level of Li-cadherin and Galectin-3 by immunohistochemistry and semiquantitative polymerase chain reaction (PCR), and correlated this with clinicopathologic parameters in 91 cases of gastric cancer. The correlation between expression levels of Li-cadherin and Galectin-3 was analyzed by Spearman correlation analysis. The expression level of Li-cadherin mRNA was correlated to differentiation and lymph node metastasis, and the expression level of Galectin-3 was related to TNM staging, differentiation and lymph node metastasis. On Spearman correlation analysis, a definitive negative correlation was found between the expression levels of Li-cadherin and Galectin-3 in gastric cancerous tissues. We postulate that interaction between Li-cadherin and Galectin-3 may play an important role in the development of gastric cancer.