RESUMO
This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser
Assuntos
Animais , Humanos , Camundongos , Células A549 , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Quinase 1 de Adesão Focal/metabolismo , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/metabolismoRESUMO
Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.
Assuntos
Humanos , Autoantígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Proteínas do Citoesqueleto/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Laríngeas/metabolismo , Laringe/metabolismo , Proteínas de Membrana/metabolismo , Fosforilação , Proteína Fosfatase 2/metabolismoRESUMO
Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.
Assuntos
Animais , Camundongos , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Aminoimidazol Carboxamida/análogos & derivados , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Western Blotting , Linhagem Celular , Núcleo Celular/metabolismo , Proteína Substrato Associada a Crk/metabolismo , Citoplasma/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Losartan/farmacologia , Metformina/farmacologia , Microscopia Confocal , Podócitos/citologia , Inibidores de Proteínas Quinases/farmacologia , Ribonucleotídeos/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE@#To study the expressions of focal adhesion kinase (FAK) and phospho-FAK( p-FAK) during skin incised wound healing and the applicability of time-dependent expressions of FAK and p-FAK.@*METHODS@#The expression of FAK and p-FAK in cutaneous incised wound in mouse were investigated by immunohistochmeistry and Western blotting.@*RESULTS@#FAK and p-FAK expression were detected in polymorphonuclear cells (PMNs) in the wound and adjacent regions 3 hours post-injury. The expressions of FAK and p-FAK were detected in a large number of infiltrating PMNs and some of mononuclear cells (MNCs) from 6 to 24 hours after injury. The MNCs and fibroblastic cells (FBCs) accounted for most part of the FAK and p-FAK positive cells from 3 to 14 days after injury. The numbers of FAK-positive cells increased continuously, reaching a peak at post-injury day 3, and then started to decrease from post-injury day 5 to 14. The changes of p-FAK-positive cells were similar to that of the FAKs, and reached a peak at 12 hours after injury.@*CONCLUSION@#Both FAK and p-FAK displayed a time-dependent expression during skin incised wound healing in mouse, with p-FAK being superior to FAK. Both FAK and p-FAK may potentially be used as new markers for determination of the wound interval.