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

• Published in: Journal of cellular and molecular medicine 2019-07, Vol.23 (7), p.4569-4581
• Main Authors: Zhang, Qingyu, Yu, Shan, Lok, Samson Ian Sam, Wong, Alice Sze Tsai, Jiao, Yufei, Lee, Leo Tsz On
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Ovarian Epithelial - genetics; Carcinoma, Ovarian Epithelial - pathology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell division; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Disease Progression; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - metabolism; FAM83D; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; invasive epithelial ovarian cancer; Invasiveness; low malignant potential ovarian tumour; Metastases; Metastasis; Mice, SCID; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; molecular diagnosis; Neoplasm Invasiveness; Original; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Penicillin; Phosphorylation; Polymerase chain reaction; Principal components analysis; Proteins; Raf protein; ROC Curve; Signal Transduction; Survival Analysis; Transcriptome - genetics; Tumors; Up-Regulation - genetics
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14360

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.