mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma
Authors: Xiaoyi Hu
Jason A Koutcher
Marc Rosenblum
Pier Paolo Pandolfi
Eric C Holland
Yi Li
Journal: Neoplasia (2005)
Discipline: CLINICAL MEDICINE
Keywords: Ras; AKT; astrocytic glioblastoma multiforme; GBM; PTEN
Affiliations: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract:  Combined activation of Ras and AKT leads to the formation of astrocytic glioblastoma multiforme (GBM) in mice. In human GBMs, AKT is not mutated but is activated in approximately 70% of these tumors, in association with loss of PTEN and/or activation of receptor tyrosine kinases. Mechanistic justification for the therapeutic blockade of targets downstream of AKT, such as mTOR, in these cancers requires demonstration that the oncogenic effect of PTEN loss is through elevated AKT activity. We demonstrate here that loss of Pten is similar to AKT activation in the context of glioma formation in mice. We further delineate the role of mTOR activity downstream of AKT in the maintenance of AKT+KRas-induced GBMs. Blockade of mTOR results in regional apoptosis in these tumors and conversion in the character of surviving tumor cells from astrocytoma to oligodendroglioma. These data suggest that mTOR activity is required for the survival of some cells within these GBMs, and mTOR appears required for the maintenance of astrocytic character in the surviving cells. Furthermore, our study provides the first example of conversion between two distinct tumor types usually thought of as belonging to specific lineages, and provides evidence for signal transduction-mediated transdifferentiation between glioma subtypes. 

Retracted: No

PubPeer comments:
 Figures 5D and 6D appear to show an overlap, shown with blue boxes. ![file] , 
 This paper appears to belong to a set of (as of today) seven papers that all show very similar, and sometimes overlapping, panels with Alizarin Red-stained cells. These papers were published by different authors at different hospitals, suggesting the photos all might have originated from the same source. The papers are: * AG Gao et al., , The First Affiliated Hospital Of Soochow University, Suzhou, DOI: 10.26355 eurrev_201807_15527- https: pubpeer.com publications 65A5976CDD42166D927AF2D3BA0B56 * B Luo et al., The Affiliated Hospital (Traditional Chinese Medicine) of Southwest Medical University, Luzhou, DOI: 10.26355 eurrev_201908_18717 - https: pubpeer.com publications 20DFC925FC185C52D8BA99B153F510 * Changgong Lan et al., The First Affiliated Hospital of Jinan University, Guangzhou, DOI: 10.3892 etm.2019.8246 - https: pubpeer.com publications 1D79EA9F787AF36661079482544D12 * FB Weng et al., The Ninth Peopleu2019s Hospital of Suzhou, Suzhou, DOI: 10.26355 eurrev_201912_19759 - https: pubpeer.com publications D63F002727B3A990A4571F7D4B6F56 * GC Gao et al., The Second Affiliated Hospital of Nanchang University, Nanchang, DOI: 10.26355 eurrev_202001_20029 - https: pubpeer.com publications F04C25EBF6963C260938DF3B6BB999 * JY Li et al., Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, DOI: 10.26355 eurrev_201908_18519 - https: pubpeer.com publications 6171C86828BF72676BB2B178610093 * YC Fu et al., Health Management Center, Weifang Peopleu2019s Hospital, Weifang, DOI: 10.26355 eurrev_201908_18632 - https: pubpeer.com publications FF66C46D23036BC26668481C279E4B Here is a collage of the images from these papers. Boxes of the same color highlight panels or parts of panels that look similar. ![file] ,