Semaphorin 3 C drives epithelial-to-mesenchymal transition, invasiveness, and stem-like characteristics in prostate cells

• Published in: Scientific reports Vol. 7; no. 1; pp. 11501 - 12
• Main Authors: Tam, Kevin J., Hui, Daniel H. F., Lee, Wilson W., Dong, Mingshu, Tombe, Tabitha, Jiao, Ivy Z. F., Khosravi, Shahram, Takeuchi, Ario, Peacock, James W., Ivanova, Larissa, Moskalev, Igor, Gleave, Martin E., Buttyan, Ralph, Cox, Michael E., Ong, Christopher J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.09.2017; Nature Publishing Group
• Subjects: 13; 13/100; 13/106; 13/109; 13/31; 14/63; 38; 38/1; 38/77; 59; 631/67/395; 631/67/589/466; 631/67/71; 631/80/84/2176; Animals; Biomarkers; Cancer; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Models, Animal; Ectopic expression; Embryogenesis; Embryonic growth stage; Epithelial-Mesenchymal Transition - genetics; Gene Expression; Glioblastoma; Heterografts; Humanities and Social Sciences; Humans; Immunophenotyping; Lung cancer; Male; Mesenchyme; Metastases; Mice; multidisciplinary; Neoplasm Invasiveness; Neoplastic Stem Cells - metabolism; Pancreatic cancer; Prostate; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Science; Science (multidisciplinary); Semaphorins; Semaphorins - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11914-6

Prostate cancer (PCa) is among the most commonly-occurring cancers worldwide and a leader in cancer-related deaths. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted signalling proteins whose normal roles reside in embryogenesis and neuronal development. In this context, semaphorins help establish chemotactic gradients and direct cell movement. Various semaphorin family members have been found to be up- and down-regulated in a number of cancers. One family member, Semaphorin 3 C (SEMA3C), has been implicated in prostate, breast, ovarian, gastric, lung, and pancreatic cancer as well as glioblastoma. Given SEMA3C’s roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells. In the present study we show that ectopic expression of SEMA3C in RWPE-1 promotes the upregulation of EMT and stem markers, heightened sphere-formation, and cell plasticity. In addition, we show that SEMA3C promotes migration and invasion in vitro and cell dissemination in vivo .