Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2
Authors: Manes Santos
Ratna K Vadlamudi
Rakesh Kumar
Diep Nguyen
Liana Adam
Journal: Journal of Cellular Physiology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Heregulin; breast cancer cells; focal adhesion; phosphorylation; FAK
Affiliations: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. 

Abstract:  Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phenotype, a process that involves changes in cell motility and adhesion. Here we demonstrate that HRG differentially regulates the site-specific phosphorylation of the focal adhesion components focal adhesion kinase (FAK) and paxilin in a dose-dependent manner. HRG at suboptimal doses (0.01 and 0.1 nM) increased adhesion of cells to the substratum, induced phosphorylation of FAK at Tyr-577, -925, and induced formation of well-defined focal points in breast cancer cell line MCF-7. HRG at a dose of 1 nM, increased migratory potential of breast cancer cells, selectively dephosphorylated FAK at Tyr-577, -925, and paxillin at Tyr-31. Tyrosine phosphorylation of FAK at Tyr-397 remained unaffected by HRG stimulation. FAK associated with HER2 only in response to 0.01 nM HRG. In contrast, 1 nM HRG induced activation and increased association of tyrosine phosphatase SHP-2 with HER2 but decreased association of HER2 with FAK. Expression of dominant-negative SHP-2 blocked HRG-mediated dephosphorylation of FAK and paxillin, leading to persistent accumulation of mature focal points. Our results suggest that HRG differentially regulates signaling from focal adhesion complexes through selective phosphorylation and dephosphorylation and that tyrosine phosphatase SHP-2 has a role in the HRG signaling. 

Retracted: No

PubPeer comments:
 When Racketeer moved on from MDA to GW University, it turned out that the graduate students at GW, vis-u00e0-vis those at MDA, were made of sterner stuff. They refused to be bullied into fraud and eventually GW did the right thing. It is recorded that Racketeer found the transparent ejection by GW u201cvery public and humiliatingu201d. Shit happens. https: www.gwhatchet.com 2015 02 05 former-department-chair-sues-university-for-8-million Fortunately, given that the u201cvery public and humiliatingu201d ejection was more than justified, it is considered unlikely that meaningful quantities of government subsidised greenbacks were ever transferred. There was a time when the MD Anderson told us that it was the best cancer hospital in the world. Was it producing bizarre cancer papers with the worldu2019s worst image fabrications in Nature journals? According to some early evolved figure sleuths, yes indeed! https: pubpeer.com publications 6D45577508D8EC5D0FE64A9D094800 Even though Racketeer, a most fecund producer of dodgy scientific publications, had moved on from the MDA, the question might arise as to how many novel, groundbreaking, publications from the then worldu2019s best cancer hospital are still out there polluting the scientific literature? More questions: Do we care? Should we do anything about it? Surely nobody cites this garbage anymore? Well, figure sleuths do as figure sleuths must. We want a cleaner literature. And therefore, for this paper, Condy will begin with the lane duplication in Fig. 6C ![image] , 
 Eyeballing Fig. 5A, there is another band duplication in two adjacent lanes ![image] , 
 In the top slice of the MD Anderson ImmunoBlots (aka MAIBs) in Fig. 5A, there are some curiously straight edges within the slice. Have bands been pasted in to lanes 3 and 6? Straight horizontal edges are particularly naughty in blottish image creations. FIJI LUT Smart might help us to see the issues. ![image] , 
 It turns out that the authors of this paper cannot count up to 10. In Fig. 4A, there are nine lanes in the MD Anderson ImmunoBlots (aka MAIBs), at least according to the labelling. However, for AKT, there are clearly 10 bands. Probably also for Phos-AKT 473, whatever that might mean. Here is Fig 4A, totally unmarked. In the unlikely event that you can actually be bothered, do please count the number of bands for yourself. ![image] , 
 In Fig. 1D, it is surprisingly true that the Y axes are correctly labelled as u201cArbitrary unitsu201d. For in lanes 3 and 4, all the MD Anderson ImmunoBlots (aka MAIBs), of which there are four, have duplicate bands in the adjacent lanes. Whereas, the bar charts for these lanes are slightly different. And therefore the u201cArbitrary unitsu201d are indeed very arbitrary. ![image] ,