Abstract
BackgroundIntra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality. Moreover, metastasis is the leading cause of death of patients with cervical cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen and its expression can be induced by hypoxia and TGF-β1. Specifically, PLOD2 is up-regulated in several types of cancer, including cervical cancer, and is associated with cancer metastasis. Thus, in this research, we aimed to investigate the role of PLOD2 in the motility of cervical cancer cells and to show the molecular mechanism underlying this effect.MethodssiRNA was used to knockdown PLOD2 in the cervical cancer cell lines HeLa and SiHa. The ability of cells to migrate and invade, their adhesion to type I collagen, and their capacity for epithelial-to-mesenchymal transition (ΕΜΤ) and focal adhesion formation were analyzed. Gene expression changes were validated by qRT-PCR, Western blotting and Immunocytochemistry. The morphological status of cells was examined using phalloidin staining. Differences in PLOD2 expression among patients with cervical cancer were identified by referring to public databases, including Oncomine and TCGA.ResultsHypoxia and TGF-β1 enhanced the expression of PLOD2 in HeLa and SiHa cells, and knockdown of PLOD2 inhibited cell motility and EMT. Moreover, the depletion of PLOD2 attenuated hypoxia-mediated cell migration and invasion and inhibited TGF-β1-induced phenotypic EMT-like changes by preventing β-catenin from entering the nucleus. In addition, PLOD2 depletion decreased cell adhesion to extracellular collagen by inhibiting the formation of focal adhesions. Moreover, a database analysis showed that PLOD2 expression is associated with human cervical cancer progression.ConclusionsOverall, our results indicated that hypoxia- and TGF-β1-induced PLOD2 expression promotes the migratory, invasive and adhesive capacities of cervical cancer cells by participating in TGF-β1 induced EMT and the formation of focal adhesions.
Highlights
Intra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality
Overall, our results indicated that hypoxia- and TGF-β1-induced PLOD2 expression promotes the migratory, invasive and adhesive capacities of cervical cancer cells by participating in TGF-β1 induced epithelial-to-mesenchymal transition (EMT) and the formation of focal adhesions
Depletion of PLOD2 inhibits mobility of cervical cancer cells As previously reported, PLOD2 expression strongly correlates with metastasis in several types of cancer, such as sarcoma, breast cancer and lung cancer [14, 16, 26]
Summary
Intra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality. Metastasis is the leading cause of death of patients with cervical cancer. PLOD2 is upregulated in several types of cancer, including cervical cancer, and is associated with cancer metastasis. In this research, we aimed to investigate the role of PLOD2 in the motility of cervical cancer cells and to show the molecular mechanism underlying this effect. Cervical cancer is the third most common cancer in women worldwide [1], and the incidence rate and mortality of this disease are higher in developing countries than in developed countries [2]. Metastases to the pelvic lymph nodes and especially the para-aortic lymph nodes are associated with poorer survival [5]. Biomarkers to accurately predict metastases are currently not available
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
