The membrane-associated form of cyclin D1 enhances cellular invasion

Chen, K; Jiao, X; Ashton, A; Di Rocco, A; Pestell, TG; Sun, Y; Zhao, J; Casimiro, MC; Li, Z; Lisanti, MP; McCue, PA; Shen, D; Achilefu, S; Rui, H; Pestell, RG

Abstract

The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1–S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1–S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.

• Journal Article Type: Article
• Acceptance Date: Sep 2, 2020
• Online Publication Date: Sep 18, 2020
• Publication Date: Sep 18, 2020
• Deposit Date: Sep 21, 2020
• Publicly Available Date: Sep 21, 2020
• Journal: Oncogenesis
• Electronic ISSN: 2157-9024
• Publisher: Nature Publishing Group
• Volume: 9
• Pages: 83
• DOI: https://doi.org/10.1038/s41389-020-00266-y
• Keywords: Article, /631/67/1347, /631/80/86, /631/80/84, /13/31, /13/51, /13/106, /13/109, /14/19, /14/33, /14/34, /14/35, /64/60, /82/29, article
• Publisher URL: https://doi.org/10.1038/s41389-020-00266-y
• Related Public URLs: http://www.nature.com/oncsis/index.html
• Additional Information: Additional Information : ** From Springer Nature via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2157-9024 **Article IDs: publisher-id: s41389-020-00266-y; manuscript: 266 **History: online 18-09-2020; published_online 18-09-2020; registration 05-09-2020; accepted 02-09-2020; collection 09-2020; rev-recd 22-08-2020; submitted 27-01-2020; Funders : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI);U.S. Department of Defense (United States Department of Defense);U.S. Department of Health & Human Services | National Institutes of Health (NIH); Projects : R01CA132115;W81XWH1810605;P30 CA10815;R01CA188575; Grant Number: R01CA132115; Grant Number: W81XWH1810605; Grant Number: P30 CA10815; Grant Number: R01CA188575