Identification of alpha-actinin 4 and 67 kDa laminin receptor as stage-specific markers in esophageal cancer via proteomic approaches.
ABSTRACT Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in the world with a very poor prognosis. The majority of ESCC patients present with advanced metastatic disease upon diagnosis. Therefore, it is important to understand the molecular mechanism in the tumor invasion process and to find new biomarkers for early diagnosis and prognostic evaluation.
Differentially expressed proteins among different stages of primary ESCCs and their matched surrounding normal tissues were compared by proteomics-based technology. The correlations between interesting proteins and clinical features of ESCC were further investigated by using ESCC tissue microarray (TMA) by immunohistochemical staining.
Compared with normal tissues, a total of 18 differentially expressed proteins were identified in ESCC in this study. Among them, expression levels of alpha-actinin 4 (ACTN4) and 67 kDa laminin receptor (67LR) were progressively increased from stage I to III. Clinicopathological correlation using TMA revealed that overexpression of ACTN4 was significantly associated with advanced tumor stage (P = .026) and lymph node metastasis (P = .049), whereas overexpression of 67LR was significantly correlated with advanced tumor stage (P = .019) but not lymph node metastasis.
These findings suggested that overexpression of ACTN4 and 67 LR is associated with ESCC progression and that these biomarkers may potentially be useful to prognostic evaluation, molecular biological classification, and therapeutic targeting.
Chapter: Proteomics and Esophageal Cancer03/2012; , ISBN: 978-953-51-0223-6
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ABSTRACT: The interaction between α-actinin and palladin, two actin-cross-linking proteins, is essential for proper bidirectional targeting of these proteins. As a first step toward understanding the role of this complex in organizing cytoskeletal actin, we have characterized binding interactions between the EF-hand domain of α-actinin (Act-EF34) and peptides derived from palladin and generated an NMR-derived structural model for the Act-EF34/palladin peptide complex. The critical binding site residues are similar to an α-actinin binding motif previously suggested for the complex between Act-EF34 and titin Z-repeats. The structure-based model of the Act-EF34/palladin peptide complex expands our understanding of binding specificity between the scaffold protein α-actinin and various ligands, which appears to require an α-helical motif containing four hydrophobic residues, common to many α-actinin ligands. We also provide evidence that the Family X mutation in palladin, associated with a highly penetrant form of pancreatic cancer, does not interfere with α-actinin binding.Journal of Molecular Biology 09/2011; 413(3):712-25. · 4.00 Impact Factor
Article: The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma.[show abstract] [hide abstract]
ABSTRACT: Protein kinase C epsilon (PKCε), an oncogene overexpressed in several human cancers, is involved in cell proliferation, migration, invasion, and survival. However, its roles in clear cell renal cell carcinoma (RCC) are unclear. This study aimed to investigate the functions of PKCε in RCC, especially in clear cell RCC, to determine the possibility of using it as a therapeutic target. By immunohistochemistry, we found that the expression of PKCε was up-regulated in RCCs and was associated with tumor Fuhrman grade and T stage in clear cell RCCs. Clone formation, wound healing, and Borden assays showed that down-regulating PKCε by RNA interference resulted in inhibition of the growth, migration, and invasion of clear cell RCC cell line 769P and, more importantly, sensitized cells to chemotherapeutic drugs as indicated by enhanced activity of caspase-3 in PKCε siRNA-transfected cells. These results indicate that the overexpression of PKCε is associated with an aggressive phenotype of clear cell RCC and may be a potential therapeutic target for this disease.Journal of Experimental & Clinical Cancer Research 09/2011; 30:88. · 2.15 Impact Factor