Universität zu Köln

Alves, Cleidson P., Dey-Guha, Ipsita, Kabraji, Sheheryar ORCID: 0000-0002-5315-7103, Yeh, Albert C., Talele, Nilesh P., Sole, Xavier, Chowdhury, Joeeta, Mino-Kenudson, Mari, Loda, Massimo, Sgroi, Dennis, Borresen-Dale, Anne-Lise, Russnes, Hege G., Ross, Kenneth N. and Ramaswamy, Sridhar (2018). AKT1(low) Quiescent Cancer Cells Promote Solid Tumor Growth. Mol. Cancer Ther., 17 (1). S. 254 - 264. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-8514

Full text not available from this repository.

Abstract

Human tumor growth depends on rapidly dividing cancer cells driving population expansion. Even advanced tumors, however, contain slowly proliferating cancer cells for reasons that remain unclear. Here, we selectively disrupt the ability of rapidly proliferating cancer cells to spawn AKT1(low) daughter cells that are rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using beta 1-integrin activation and the AKT1-E17K-mutant oncoprotein as experimental tools in vivo. Surprisingly, we find that selective depletion of AKT1(low) slow proliferators actually reduces the growth of a molecularly diverse panel of human cancer cell xenograft models without globally altering cell proliferation or survival in vivo. Moreover, we find that unusual cancer patients with AKT1-E17K-mutant solid tumors also fail to produce AKT1(low) quiescent cancer cells and that this correlates with significantly prolonged survival after adjuvant treatment compared with other patients. These findings support a model whereby human solid tumor growth depends on not only rapidly proliferating cancer cells but also on the continuous production of AKT1(low) slow proliferators. (C) 2017 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alves, Cleidson P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dey-Guha, Ipsita UNSPECIFIED UNSPECIFIED UNSPECIFIED Kabraji, Sheheryar UNSPECIFIED orcid.org/0000-0002-5315-7103 UNSPECIFIED Yeh, Albert C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Talele, Nilesh P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sole, Xavier UNSPECIFIED UNSPECIFIED UNSPECIFIED Chowdhury, Joeeta UNSPECIFIED UNSPECIFIED UNSPECIFIED Mino-Kenudson, Mari UNSPECIFIED UNSPECIFIED UNSPECIFIED Loda, Massimo UNSPECIFIED UNSPECIFIED UNSPECIFIED Sgroi, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Borresen-Dale, Anne-Lise UNSPECIFIED UNSPECIFIED UNSPECIFIED Russnes, Hege G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ross, Kenneth N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramaswamy, Sridhar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-204824
DOI:	10.1158/1535-7163.MCT-16-0868
Journal or Publication Title:	Mol. Cancer Ther.
Volume:	17
Number:	1
Page Range:	S. 254 - 264
Date:	2018
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1538-8514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STEM-CELLS; AKT1(E17K); ACTIVATION; MECHANISMS; DORMANCY; MUTATION; JARID1B; KINASE; AKT1 Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20482