Abstract
In Taiwan, Cervical cancer (CC) is the 7th leading cause of death in female cancer. Moreover, according to the WHO's report in 2011, cervical cancer is the third highest cancer incidence in female, around 530,000 new cases of cervical cancer were diagnosed each year with high death rate. The reason for a high mortality of cervical cancer is mainly due to cancer metastasis. When cervical cancer is diagnosed in early stage, the five-year survival rate is very high, but once metastasis occurs, the five-year survival rate reduced significantly. Thus, to manage cervical cancer, finding metastasis biomarkers and understanding the mechanisms are critical. In our current study, we used a pair of cervical adenocarcinoma cell lines, HeLa and its invasive partner, HeLa-I5, as a model system to examine invasive mechanism and find out the potential cellular targets associated with metastasis. We use two-dimensional differential gel electrophoresis difference (2D-DIGE), matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify differentially expressed proteins between HeLa and HeLa-I5. Our proteomics study revealed that 68 proteins show significant difference between the two lines and some of the identified proteins have been validated through immunoblotting. Further study by using RNA interference (RNAi) technique, we found progesterone receptor membrane component1 (PGRMC1) protein is a key player in response to cervical cancer invasion, migration and proliferation. Our data demonstrated that the invasive ability and the migration ability decreased for 2-fold and 1.7-fold, respectively, in the process of PGRMC1 knockdown. To sum up, PGRMC1 has been evidenced to modulate cervical cancer migration, invasion and proliferation. Our data also provided useful diagnostic markers and therapeutic candidates for the treatment of cervical cancer invasion and migration.