RETRACTED ARTICLE: Inhibition of Tumor Angiogenesis by Tumstatin: Insights into Signaling Mechanisms and Implications in Cancer Regression
Authors: Akulapalli Sudhakar
Chandra S Boosani
Journal: Pharmaceutical Research (2008)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: tumors; angiogenesis; cancer; endogenous angiogenesis inhibitors; type IV collagen
Affiliations: Cell Signaling and Tumor Angiogenesis Laboratory, Department of Genetics, Boys Town National Research Hospital, Omaha, NE 68131, USA. 

Abstract:  Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led to the identification of endogenous angiogenesis inhibitors generated from type IV collagen, a major component of vascular basement membrane (VBM). Type IV collagen and the angiogenesis inhibitors derived from it are involved in complex roles, than just the molecular construction of basement membranes. Protease degradation of collagens in VBM occurs in various physiological and pathological conditions and produces several peptides. Some of these peptides are occupied in the regulation of functions conflicting from those of their original integral molecules. Tumstatin (alpha3(IV)NC1), a proteolytic C-terminal non-collagenous (NC1) domain from type IV collagen alpha3 chain has been highlighted recently because of its potential role in anti-angiogenesis, however its biological actions are not limited to these processes. alpha3(IV)NC1 inhibits proliferation by promoting endothelial cell apoptosis and suppresses diverse tumor angiogenesis, thus making it a potential candidate for future cancer therapy. The present review surveys the physiological functions of type IV collagen and discovery of alpha3(IV)NC1 as an antiangiogenic protein with a comprehensive overview of the knowledge gained by us towards understanding its signaling mechanisms. 

Retracted: Yes

PubPeer comments:
 2021 retraction notice. https: link.springer.com article 10.1007 s11095-020-02974-x The Editor-in-Chief has retracted this article [1]. A report by the US Office of Research Integrity has concluded that the image shown as the protein band tumstatin (u03b13(IV)NC1) in Fig. 2 (lanes 2u20134) was also used in [2] to represent a different experiment. The Editor-in-Chief therefore no longer has confidence in the conclusions presented in this article. Akulapalli Sudhakar does not agree with this retraction. The Editor-in-Chief was not able to obtain a current email address for Chandra S Boosani. References 1. Akulapalli Sudhakar Chandra S. Boosani. Inhibition of Tumor Angiogenesis by Tumstatin: Insights into Signaling Mechanisms and Implications in Cancer Regression. Pharm Res 25, 2731 (2008). https: doi.org 10.1007 s11095-008-9634-z 2. Akulapalli Sudhakar, Aruna Ramachandran, Sudip Ghosh Seyed E. Hasnain, Randal J. Kaufman and Kolluru V. A. Ramaiah. Phosphorylation of Serine 51 in Initiation Factor 2u03b1 (eIF2u03b1) Promotes Complex Formation between eIF2u03b1(P) and eIF2B and Causes Inhibition in the Guanine Nucleotide Exchange Activity of eIF2B. Biochemistry 2000; 39(42):12929-12938 ,