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FAM83D promotes ovarian cancer progression and its potential application in diagnosis of invasive ovarian cancer.

ABSTRACT: Although invasive epithelial ovarian cancer (IOC) and low malignant potential ovarian tumour (LMP) are similar, they are associated with different outcomes and treatment strategies. The current accuracy in distinguishing these diseases is unsatisfactory, leading to delays or unnecessary treatments. We compared the molecular signature of IOC and LMP cases by analysing their transcriptomic data and re-clustered them according to these data rather than the pathological dissection. We identified that FAM83D was highly expressed in IOC. To verify the role of FAM83D in the progression and metastasis, we used the isogenic ovarian cancer metastatic models, highly metastatic cells (HM) and non-metastatic cells (NM). Overexpression of FAM83D significantly promoted cell proliferation, migration and spheroid formation. This was consistent with previous data showing that high FAM83D expression is associated with poor prognosis in cancer patients. Moreover, similar to the HM cells, the FAM83D-overexpressing NM cells demonstrated stronger phosphorylation of the epidermal growth factor receptor (EGFR) and c-Raf. This indicates that the action of FAM83D is mediated by the activation of the EGFR pathway. Taken together, this report suggested that FAM83D might be an excellent molecular marker to discriminate between IOC and LMP.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6584551 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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FAM83D promotes ovarian cancer progression and its potential application in diagnosis of invasive ovarian cancer.

Zhang Qingyu Q Yu Shan S Lok Samson Ian Sam SIS Wong Alice Sze Tsai AST Jiao Yufei Y Lee Leo Tsz On LTO

Journal of cellular and molecular medicine 20190430 7

Although invasive epithelial ovarian cancer (IOC) and low malignant potential ovarian tumour (LMP) are similar, they are associated with different outcomes and treatment strategies. The current accuracy in distinguishing these diseases is unsatisfactory, leading to delays or unnecessary treatments. We compared the molecular signature of IOC and LMP cases by analysing their transcriptomic data and re-clustered them according to these data rather than the pathological dissection. We identified tha ...[more]

PMID: 31037837

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Project description:BackgroundTBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition.MethodsThe relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells.ResultsTBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness.ConclusionsOverall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions.

Dataset Information

FAM83D promotes ovarian cancer progression and its potential application in diagnosis of invasive ovarian cancer.

Publications

FAM83D promotes ovarian cancer progression and its potential application in diagnosis of invasive ovarian cancer.

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