Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice
Authors: Yang Wang
Liyan Xue
Mingrong Wang
Rong Liu
Xiao Yang
Lihui Zuo
Ning Lu
Qimin Zhan
Shujuan Shao
Ning Hou
Yongmei Song
Journal: Journal of Clinical Investigation (2010)
Discipline: CLINICAL MEDICINE
Keywords: Mitotic events; Genomic instability; Mutator phenotypes; Ninein-like protein (Nlp); BRCA1-associated
Affiliations: State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Abstract:  Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target. 

Retracted: No

PubPeer comments:
 Figure 12. * Red boxes: parts of lanes B look very similar to each other. I realize that these both represent live bacterial samples but I would not expect two lanes to look this similar, even if the same sample was loaded twice. Maybe I am seeing ghosts? * Green circles: an area with two dots appears to be visible multiple times in the top of the gel.  , 
 Tables. Some standard deviation values appear to be visible more often than expected. The results also look like they display means + - SD of 3 measurements, while each group contained 10 rats. For example, three measurements of 7,8,8 will give a mean of 7.67 and an average of 0.58. The repetitive value of 0.58 and 1.53 suggests that the 3 measurements were also very similar to each other, which is unexpected in biological measurements. Could the authors please provide the raw measurements (before mean and SD was calculated)?  , 
 #1 Regarding comment Red boxes: parts of lanes B look very similar to each other. I realize that these both represent live bacterial samples but I would not expect two lanes to look this similar, even if the same sample was loaded twice. Maybe I am seeing ghosts? . These two lanes came from the bacterial sample. What do you expect to see the protein pattern when you have uploaded the same volumes from the same sample?. Definitely, you will see the same number of protein bands in both lanes. It seems such comment came from person hasn t expertise in the experimental works. Regarding comment Some standard deviation values appear to be visible more often than expected . That what we had obtained after performing statistical analysis. , 
 #3 Even without expertise with the experimental methods, the repetitions noted by Dr. Bik seem potentially to have occurred via photo editing rather than experimental conditions. Perhaps the authors can provide a high resolution photo from this figure to reassure readers. Please upload to https: imgur.com if size limitations prevent doing so here. , 
 Dear Dr. Sheweita, thank you for your reply. I would say that anyone with expertise in the experimental works - or with expertise in biomedical image analysis - would know that loading the same sample in two adjacent lanes in a gel would result in two banding patterns that are each unique. The lanes will indeed look similar in terms of number and size of bands, but with unique features in each individual band and lane. That is not the case here. I am also a bit taken aback by your unwillingness to share the original data for the measurements in Tables 1-3. Do you have the original data and would you be willing to share this here? A link to a Google drive or Dropbox folder would be wonderful. , 
 Dear author - There are typos in Tables 1, 2 and 3. Routs should be **Routes**. raw should be **row**. INF-gamma should be** IFN-gamma**. I think it will help to proof-read the article carefully and identify any other errors to request their correction with the journal. , 
 #6 #5 Dear Dr Thank you so much on your comments. , 
 #2 this paper has been reviewed by three reviwers before publishing. , 
 #8 Dr. Sheweita: I donu2019t think anyone here suggests that the paper wasnu2019t peer reviewed, but the fact that errors and fabrications - although this may not be the case here - survive the peer review process in many research papers is well known and uncontroversial. The original data should be readily available for a paper published about a year ago. Are you unwilling to share that data here? Would you be able to share it with the journal (upon request), or is the original data now missing? , 
 #2 I will check the original data and let you know , 
 Any updates, Dr. Sheweita? We would love to see the original data. , 
 #11 Figure 4 may also have issues. Do you concur? ***  , 
 Figure 13 might have some issues too.  ,