PTTG promotes invasion in human breast cancer cell line by upregulating EMMPRIN via FAK/Akt/mTOR signaling
Authors: Jianjun Peng
Jing Xie
Hui Gao
Feng Zhong
Zhiwu Han
Journal: American journal of cancer research (2016)
Discipline: CLINICAL MEDICINE
Keywords: EMMPRIN; FAK; PTTG; breast cancer; metastasis.
Affiliations: Qingdao University Qingdao, Shandong 266071, China., College of Life Sciences, Chongqing Normal University Chongqing 401331, China., Qingdao UniversityQingdao, Shandong 266071, China; Qingdao University Affiliated HospitalQingdao, Shandong 266071, China.

Abstract:  Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed at higher level in most of the tumors. PTTG overexpression correlates with lymph node infiltration and a higher degree of tumor recurrence in breast cancer. However, the cellular functions and precise signals elicited by PTTG in breast cancer are not fully understood. Here, we established a breast cancer cell line which stably overexpressed PTTG. In vitro experiments showed that overexpression of PTTG in MCF-7 cells was associated with enhanced cell migration and invasion as well as EMT. Our results also demonstrated that PTTG overexpression correlated with elevated EMMPRIN level, which mediated the enhanced cell migration, invasion and EMT. Moreover, our findings suggested that PTTG enhances metastatic potential of breast cancer cells by inducing EMMPRIN through activating FAK/Akt/mTOR pathway. Our findings may lead to a better understanding of the biological effect of PTTG and provide mechanistic insights for developing potential therapeutic strategies for inhibiting the invasion and metastasis of breast cancer. 

Retracted: No

PubPeer comments:
 Upper left, Fig 2 from Chen et al (2017); lower left, Fig 2 from Ding et al (2016). At right, Fig 3A:  PTTG overexpression promotes EMT process. A. Effect of PTTG overexpression on cell morphology was evaluated by fluorescent microscopy .  , 
 Fig 8 B. Overlap of invasion assay images.  , 
 Fig 8C,  Inhibitors of FAK Akt mTOR signaling pathway significantly abolished the changes in EMT marker expressions induced by PTTG. The representative western blot is shown. At right, Fig 6C from [Han et al (2016)] :  ROS AMPK activator and GSK3u03b2 inhibitor mimicked the suppressing effect of physcion on EMT, whereas ROS AMPK inhibitor abolished the suppressive effect of physcion on EMT. The concentrations of AICAR, Compound C, LiCl, NAC and CoCl2 were 5 mmol L, 10 u03bcmol L, 10 mmol L, 5 mmol L and 100 u03bcmol L, respectively .  , 
 At right, Fig 1C:  Transfection of PTTG overexpressing plasmid and confirmation of overexpressing PTTG in MCF-7 cells. ... C. The expression of PTTG protein was detected with western blots. At left, Fig 6B from [Chen et al (2015)] :  Physcion suppresses HIF-1u03b1 expression via activating AMPK signaling. The HCT116 cells were incubated with physcion at the indicated concentrations (or 5 u03bcM if not marked) for 48h....B. Western blots showed the involvement of AMPK signaling in the modulatory effect of physcion on HIF-1u03b1 and EMMPRIN level. Centre, Fig 5B from [Han et al (2016)] :  Involvement of ROS AMPK GSK3u03b2 signaling in the modulatory effect of physcion on SOX2. SW620 cells were incubated with physcion at the indicated concentrations (or 5 u03bcmol L if not marked) for 24 h.... (B) Physcion modulated expression of SOX2 via AMPK GSK3u03b2 signaling.  , 
 Fig 8D. At right, 5D from [Wang et al (2018)] :  RLIP76 is a direct target of miR-137 in ccRCC cells. ... D). MiR-137 expression in ccRCC tissue has a negative association with protein expression of RLIP76 in CRC specimen.  Possible re-use of a loading control. , 
 Below, Fig 2B:  Increase PTTG expression enhances MCF-7 cell migration and invasion in vitro. ... B. Cell invasion after transfection was determined by Transwell assay . Above, Fig 2B of [Xie et al (2015)] :  Hispidulin suppresses hypoxia-induced migration (A) and invasion (B) in HT-29 cells.   Both papers have been cited elsewhere, so I figure that it is worth pointing out the duplicated images. , 
 Corrected [1 April 2020] . Retracted [1 July 2020] .  A large portion of the data and the text in this article was copied from another source as disclosed by a knowledgeable informant and subsequently confirmed by the Editorial Office. Therefore, the entire article has been retracted in accordance with this journalu2019s policy and editorial decision. , 
 http: www.most.gov.cn zxgz kycxjs kycxgzdt 202201 t20220127_179206.html Google Translated Date: January 27, 2022 14:44 Source: Ministry of Science and Technology u3000u300017. The paper  PTTG promotes invasion in human breast cancer cell line by upregulating EMMPRIN via FAK Akt mTOR signaling by Han Zhiwu from Qingdao University Affiliated Hospital as the corresponding author and Gao Hui from the School of Pharmacy as the first author. After investigation, the paper was found to be fraudulent. Han Zhiwu (merged with the other two papers) will be dealt with as follows: demerit for 1 year, cancellation of application or application for science and technology projects (special projects, funds, etc.), science and technology awards, and qualifications for science and technology talent titles for 7 years, cancel as a nominee or recommender , Nominated or recommenders, review experts and other qualifications for 7 years, recorded in the file of scientific research integrity and dishonesty, given a scientific research integrity admonishment talk, canceled from participating in this year s evaluation, and the annual evaluation shall not be determined as qualified or above; for Gao Hui ( It will be dealt with as follows: demerit for 1 year, cancel application or application for science and technology projects (special projects, funds, etc.), science and technology awards, and qualifications for science and technology talent titles for 9 years, cancel as a nominee or recommender, be nominated Or recommenders, review experts and other qualifications for 9 years, recorded in the file of scientific research integrity and dishonesty, canceled from participating in the current year s evaluation, and the annual evaluation shall not be determined as qualified or above. u3000u3000(Notification link: https: kjc.qdu.edu.cn info 1023 3178.htm) ,