BMP4-Smad signaling pathway mediates adriamycin-induced premature senescence in lung cancer cells
Authors: Hui Huang
Baiqu Huang
Jun Lu
Yunpeng Feng
Xuefang Han
Lina Pan
Dongmei Su
Shan Zhu
Yu Zhang
Guoling Ren
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell senescence; premature senescence; adriamycin; BMP4; NSCLC
Affiliations: Institute of Genetics and Cytology and Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China.

Abstract:  Cell senescence, an irreversible cell cycle arrest, reflects a safeguard program that limits the capacity of uncontrolled cell proliferation. Treatment of tumor cells with certain chemotherapeutic agents activates premature senescence to decrease the tumorigenecity. Here we show that sublethal concentrations of adriamycin could induce premature senescence in lung cancer cells. Adriamycin treatment resulted in the up-regulation of BMP4, which is underexpressed in NSCLC (non-small cell lung cancers). Moreover, the BMP4-Smad pathway played a key role in mediating adriamycin-induced senescence. Overexpression of BMP4 was able to induce premature senescence in lung cancer cells and this process required the participation of cyclin/cyclin-dependent kinase (cdk) inhibitors p16(INK4a) and p21(WAF1/cip1). We also show that increases of p16(INK4a) and p21(WAF1/cip1) expression in response to BMP4 were mediated by the Smad signaling pathway. Furthermore, our data revealed that p300 was recruited to P16(INK4a) and P21(WAF1/cip1) promoters by Smad1/5/8 to induce the hyperacetylation of histones H3 and H4 at the promoters. The present study provides useful clues to the evaluation of the potentiality of BMP4 as a responsive molecular target for cancer chemotherapy. 

Retracted: No

PubPeer comments:
 In Figure 3, a gel is reused for different samples. ![file] , 
 In Figure 4, parts of the blot were duplicated, and the lower parts are duplicated and mirrored. ![file] , 
 2019 retraction. http: www.jbc.org content 294 35 13200 This article has been withdrawn by Magdalena Migocka, Ewelina Posyniak, Ewa Maciaszczyk-Dziubinska, and Anna Kosieradzaka. Anna Papierniak could not be reached. The CsCACS gels in Fig. 3 (A and B) were duplicated. The following were found in Fig. 4. The CsHMA5.1 immunoblot was inappropriately manipulated. Lanes 6 and 7 of the CsHMA5.2 immunoblot were duplicated. Lanes 1 and 2 of the PM H-ATPase immunoblot and lanes 6u20139 of the PPase immunoblot are the same. Additionally, lane 8 of the PM H-ATPase immunoblot was reused in lane 1 of the PPase immunoblot. Lanes 3u20136 of the PM H-ATPase immunoblot were rotated 180u00b0 and reused as lanes 2u20135 of the PPase immunoblot. Finally, the markers were reused between the PM H-ATPase and PPase immunoblots. Fig. 5 (A and B) contained many repeating features. In Fig. 8B, the first four colonies in the dilution series for the upper control CsHMA5.2 were reused in the lower control vector dilution series. Additionally, in the lower control panel, the rightmost in the dilution series was duplicated between vector and CsHMA5.2. Finally, some colonies shown in Fig. 8B and the V-PPase immunoblot in Fig. 9B were previously published in J. Exp. Bot. 2015 66:1001u20131015, representing different experimental conditions. , 
 Even though this paper was retracted more than 1 year ago, the authors maintain an unretracted copy on ResearchGate, allowing it to be cited: https: www.researchgate.net publication 276210188 ,