Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer

Abstract

MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH 2 kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P < 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer.

P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration

“…Two types of PAKs have significant differences in the structure and function. The PAK1 gene is localized within the 11q13 region, and 11q13.5-q14 amplifications involving the PAK1 locus are found in the bladder [11], ovary [12], and breast [13] cancer. Several reports have addressed the clinical correlation between PAK1 overexpression and metastasis, invasion, or progression of cancers [14e18].…”

“…Several reports have addressed the clinical correlation between PAK1 overexpression and metastasis, invasion, or progression of cancers [14e18]. Julia et al [7] reported that PAK1 was increased in colorectal cancer and associated with progression and metastasis; Siu et al [12] reported that PAK1 and PAK2 play important roles in carcinogenesis and may be potential prognostic markers in ovarian cancer. In addition, PAK1 overexpression seemed to be associated with metastasis of gastric cancer [14].…”

Death Domain-associated Protein DAXX Promotes Ovarian Cancer Development and Chemoresistance

“…The high mortality rate associated with this disease may be attributable to its late diagnosis and the complications that arise from metastasis (19). Unlike most carcinomas that rely on the vasculature for metastasis, an early event in ovarian cancer dissemination is the shedding of cells from the primary tumor into the peritoneal cavity followed by diffuse "seeding" of the peritoneal cavity (20). This unique metastatic mechanism presents a distinct set of therapeutic challenges.…”

Verification of a biomarker discovery approach for detection of Down syndrome in amniotic fluid via multiplex selected reaction monitoring (SRM) assay

“…Little is known about the functions of MUC13 other that its involvement in barrier functions of epithelium. Abnormal expression of MUC13 has been linked to gastric, colon, and ovarian cancer, as well as ulcerative colitis [28][29][30]. Further investigation on the functions and expression of MUC13 during fetal development will allow us to understand its potential involvement in DS pathogenesis.…”