Endocrine Abstracts (2014) 35 OC10.3 | DOI: 10.1530/endoabs.35.OC10.3

The NMU signaling controls cancer progression of human RL95-2 endometrial cancer cells through cell motility maintenance

Ting-Yu Lin & Ching-Wei Luo

Genome Sciences, Taipei, Taiwan.

In addition to regular functions in controlling muscle contraction and energy homeostasis, recent studies have reported the neuromedin U (NMU) signaling plays important roles in cancer progression. Intriguingly, we observed that both NMU and one of its receptors, NMUR2, are highly expressed and co-localized in the mouse uterine endometrial luminal epithelium during the estrus stage. We also found that the NMU transcript is dramatically augmented in patients with high-grade endometrial cancers, suggesting that the NMU signaling may participate in the uterine cancer progression. Following these findings, RL95-2 and Ishikawa cells, the endometrial cancer lines with a high NMU transcript level, are used to investigate the roles of NMU signaling during endometrial cancer progression. Using NMU knockdown approaches, we demonstrated that the high level of NMU signaling is required for the maintenance of cell morphology and the ability of migration and invasion in RL95-2 cells, which is derived from the moderately-differentiation endometrial cancer, but not in the Ishikawa cells, which is derived from the well-differentiation endometrial cancer. Further, we found that NMU knockdown in RL95-2 cells not only decreases the basal transcripts but also attenuates the EGF- or TGFβ-induced levels of N-cadherin and vimentin, which are required for maintenance of cell morphology and cell motility. Low motility rate might dampen the spreading efficiency, restrict the growth space, and thus affect the growth rate of RL95-2 cells. Indeed, we did observe that RL95-2 cells with NMU knockdown grew in clusters and have a lower growth rate than the control cells under a prolonged culture condition. Taken together, these results suggest that the NMU signaling is critical for high-grade endometrial cancers and involved in the cancer progression through the regulation of cell motility.

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