New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31–5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial–mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.
Fei Han, Wen-bin Liu, Jian-jun Li, Ming-qian Zhang, Jun-tang Yang, Xi Zhang, Xiang-lin Hao, Li Yin, Cheng-yi Mao, Xiao Jiang, Jia Cao and Jin-yi Liu
Xiao-Hua Jiang, Jie-Li Lu, Bin Cui, Yong-Ju Zhao, Wei-qing Wang, Jian-Min Liu, Wen-Qiang Fang, Ya-Nan Cao, Yan Ge, Chang-xian Zhang, Huguette Casse, Xiao-Ying Li and Guang Ning
Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterized by the development of tumours of the parathyroid, anterior pituitary and pancreatic islets, etc. Heterozygous germ line mutations of MEN1 gene are responsible for the onset of MEN1. We investigated the probands and 31 family members from eight unrelated Chinese families associated with MEN1 and identified four novel mutations, namely 373_374ins18, 822delT, 259delT and 1092delC, as well as three previously reported mutations, such as 357_360delCTGT, 427_428delTA and R108X (CGA>TGA) of MEN1 gene. Furthermore, we detected a loss of heterozygosity (LOH) at chromosome 11q in the removed tumours, including gastrinoma, insulinoma and parathyroid adenoma from two probands of MEN1 families. RT-PCR and direct sequencing showed that mutant MEN1 transcripts remained in the MEN1-associated endocrine tumours, whereas normal menin proteins could not be detected in those tumours by either immunohistochemistry or immunoblotting. In conclusion, MEN1 heterozygous mutations are associated with LOH and menin absence, which are present in MEN1-associated endocrine tumours.