The membrane-associated form of cyclin D1 enhances cellular invasion

Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G. Pestell, Yunguang Sun, Jun Zhao, Mathew C. Casimiro, Zhiping Li, Michael P. Lisanti, Peter A. McCue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G. Pestell

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number83
JournalOncogenesis
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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