Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/87891
Title: Gastrin stimulates pancreatic cancer cell directional migration by activating the Gα12/13–RhoA–ROCK signaling pathway
Authors: Mu, Ganggang
Ding, Qianshan
Li, Hongyan
Zhang, Li
Zhang, Lingli
He, Ke
Wu, Lu
Deng, Yunchao
Yang, Dongmei
Wu, Lianlian
Xu, Ming
Zhou, Jie
Yu, Honggang
Keywords: Pancreatic Cancer Cell
Gastrin
DRNTU::Engineering::Electrical and electronic engineering
DRNTU::Science::Biological sciences
Issue Date: 2018
Source: Mu, G., Ding, Q., Li, H., Zhang, L., Zhang, L., He, K., et al. (2018). Gastrin stimulates pancreatic cancer cell directional migration by activating the Gα12/13–RhoA–ROCK signaling pathway. Experimental & Molecular Medicine, 50(5), 59-.
Series/Report no.: Experimental & Molecular Medicine
Abstract: The mechanism by which gastrin promotes pancreatic cancer cell metastasis is unclear. The process of directing polarized cancer cells toward the extracellular matrix is principally required for invasion and distant metastasis; however, whether gastrin can induce this process and its underlying mechanism remain to be elucidated. In this study, we found that gastrin-induced phosphorylation of paxillin at tyrosine 31/118 and RhoA activation as well as promoted the metastasis of PANC-1 cancer cells. Depletion of Gα12 and Gα13 inhibited the phosphorylation of paxillin and downstream activation of GTP-RhoA, blocked the formation and aggregation of focal adhesions and facilitated polarization of actin filaments induced by gastrin. Suppression of RhoA and ROCK also exhibited identical results. Selective inhibition of the CCKBR–Gα12/13–RhoA–ROCK signaling pathway blocked the reoriented localization of the Golgi apparatus at the leading edge of migrated cancer cells. YM022 and Y-27632 significantly suppressed hepatic metastasis of orthotic pancreatic tumors induced by gastrin in vivo. Collectively, we demonstrate that gastrin promotes Golgi reorientation and directional polarization of pancreatic cancer cells by activation of paxillin via the CCKBR–Gα12/13–RhoA–ROCK signal pathway.
URI: https://hdl.handle.net/10356/87891
http://hdl.handle.net/10220/45566
ISSN: 1226-3613
DOI: http://dx.doi.org/10.1038/s12276-018-0081-6
Rights: © 2018 The Author(s) (Nature Publishing Group). This article is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution andreproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:EEE Journal Articles

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