Progesterone receptor membrane component 1 is involved in oral cancer cell metastasis

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 17; pp. 9737 - 9751
• Main Authors: Huang, Hsun‐Yu, Chou, Hsiu‐Chuan, Law, Ching‐Hsuan, Chang, Wan‐Ting, Wen, Tzu‐Ning, Liao, En‐Chi, Lin, Meng‐Wei, Lin, Li‐Hsun, Wei, Yu‐Shan, Tsai, Yi‐Ting, Chen, Hsin‐Yi, Tan, Kui‐Thong, Kuo, Wen‐Hung, Ko, Mei‐Lan, Chang, Shing‐Jyh, Lee, Ying‐Ray, Chan, Hong‐Lin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2020; John Wiley and Sons Inc
• Subjects: Antibodies; Apoptosis; Biomarkers; Gel electrophoresis; Gene expression; Head & neck cancer; Invasiveness; Lymphatic system; Mass spectroscopy; Membrane proteins; Mesenchyme; Metastases; Metastasis; Oral cancer; Oral squamous cell carcinoma; Original; Patients; Progesterone; progesterone receptor membrane component 1; Proteins; proteomics; RNA-mediated interference; Squamous cell carcinoma; Vimentin; Vinculin; progesterone receptor membrane component 1; proteomics; metastasis; oral cancer
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.15535

Cancer metastasis is a common cause of failure in cancer therapy. However, over 60% of oral cancer patients present with advanced stage disease, and the five‐year survival rates of these patients decrease from 72.6% to 20% as the stage becomes more advanced. In order to manage oral cancer, identification of metastasis biomarker and mechanism is critical. In this study, we use a pair of oral squamous cell carcinoma lines, OC3, and invasive OC3‐I5 as a model system to examine invasive mechanism and to identify potential therapeutic targets. We used two‐dimensional differential gel electrophoresis (2D‐DIGE) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF/TOF MS) to examine the global protein expression changes between OC3 and invasive OC3‐I5. A proteomic study reveals that invasive properties alter the expression of 101 proteins in OC3‐I5 cells comparing to OC3 cells. Further studies have used RNA interference technique to monitor the influence of progesterone receptor membrane component 1 (PGRMC1) protein in invasion and evaluate their potency in regulating invasion and the mechanism it involved. The results demonstrated that expression of epithelial‐mesenchymal transition (EMT) markers including Twist, p‐Src, Snail1, SIP1, JAM‐A, vimentin and vinculin was increased in OC3‐I5 compared to OC3 cells, whereas E‐cadherin expression was decreased in the OC3‐I5 cells. Moreover, in mouse model, PGRMC1 is shown to affect not only migration and invasion but also metastasis in vivo. Taken together, the proteomic approach allows us to identify numerous proteins, including PGRMC1, involved in invasion mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of oral cancer invasion.