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

doi:10.1038/s41389-020-00266-y

The membrane-associated form of cyclin D1 enhances cellular invasion

Oncogenesis. 2020 Sep 18;9(9):83. doi: 10.1038/s41389-020-00266-y.

Authors

Ke Chen^#¹, Xuanmao Jiao^#², Anthony Ashton², Agnese Di Rocco², Timothy G Pestell¹, Yunguang Sun³, Jun Zhao², Mathew C Casimiro^{2

4}, Zhiping Li², Michael P Lisanti⁵, Peter A McCue⁶, Duanwen Shen⁷, Samuel Achilefu^{7

8

9}, Hallgeir Rui³, Richard G Pestell^{10

11}

Affiliations

¹ Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
² Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, Wynnewood, PA, 19096, USA.
³ Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁴ Dept of Science and Math, Abraham Baldwin Agricultural college, Tifton, GA, 31794, Georgia.
⁵ Biomedical Research Centre (BRC), Translational Medicine, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.
⁶ Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
⁷ Departments of Biomedical Engineering, Washington University, St. Louis, MO, 63110, USA.
⁸ Departments of Radiology, Washington University, St. Louis, MO, 63110, USA.
⁹ Departments of Biochemistry & Molecular Biophysics, Washington University, St. Louis, MO, 63110, USA.
¹⁰ Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, Wynnewood, PA, 19096, USA. Richard.pestell@bblumberg.org.
¹¹ The Wistar Cancer Center, Wistar Institute, Philadelphia, PA, 19104, USA. Richard.pestell@bblumberg.org.

^# Contributed equally.

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 D1^NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1^MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1^MEM was sufficient to induce G₁-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1^MEM 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.

Abstract

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