A Gene Expression Signature Associated with “K-Ras Addiction” Reveals Regulators of EMT and Tumor Cell Survival
Authors: Patricia Greninger
Anurag Singh
Nabeel Bardeesy
Sheila Violette
Daniel Rhodes
Jeff Settleman
Louise Koopman
Journal: Cancer Cell (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: K-ras mutations; short hairpin RNAs; lung cancer; pancreatic cancer; gene expression signature
Affiliations: Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA 94306, USA.

Abstract:  K-ras mutations occur frequently in epithelial cancers. Using short hairpin RNAs to deplete K-Ras in lung and pancreatic cancer cell lines harboring K-ras mutations, two classes were identified-lines that do or do not require K-Ras to maintain viability. Comparing these two classes of cancer cells revealed a gene expression signature in K-Ras-dependent cells, associated with a well-differentiated epithelial phenotype, which was also seen in primary tumors. Several of these genes encode pharmacologically tractable proteins, such as Syk and Ron kinases and integrin beta6, depletion of which induces epithelial-mesenchymal transformation (EMT) and apoptosis specifically in K-Ras-dependent cells. These findings indicate that epithelial differentiation and tumor cell viability are associated, and that EMT regulators in "K-Ras-addicted" cancers represent candidate therapeutic targets. 

Retracted: No

PubPeer comments:
 Coefficient values of tables of Eq. 13 and 14 (thermal conductivity and viscosity ratio, respectively) seems too coincidental to be true. How come the coefficient values of two properties that not physically-unrelated can share the same denominator value? ![file] Moreover, the authors claim that the empirical equations were taken from another paper in the literature [1]. However, such formulae are not found in the article in question. Could the authors clarify how to come up with the correlations? Lastly, some contents of Figure 3 and 8 appears to be duplicated as well. Apparently all of the temperature contours shown in the paper are also pretty useless because the isothermal lines do not even show the temperature! ![file] References: [1] Esfe, M. H., Saedodin, S., Mahian, O. Wongwises, S. Efficiency of ferromagnetic nanoparticles suspended in ethylene glycol for applications in energy devices: Effects of particle size, temperature, and concentration.u00a0Int. Commun. Heat Mass Transf.u00a058, 138u2013146 (2014). [doi.org 10.1016 j.icheatmasstransfer.2014.08.035] , 
 **Reference [21] is irrelevant to the subject.** ![file] ![file] , 
 **Reference [24] is not relevant to the subject.** ![file] ![file] , 
 **Reference [20] is not directly relevant to the subject.** ![file] ![file] , 
 **Reference [22] is not relevant to the subject.** ![file] ![file] , 
 **Reference [23] is not relevant to the subject.** ![file] ![file] , 
 The fact that the text just says _References_, rather than the author s name as in the case of the relevant references, suggests that these references were added after submission, not by the authors. ![file] ![file] , 
 **Reference [25] is not directly relevant to the subject of the article.** ![file] ![file] , 
 References [36] and [37] are not relevant to the subject. ![file] ![file] ----------------------------------------------------------------------------------------------- ![file] , 
 Reference [38] does not support the claimed *Empirical Equations* shown in the tables below. ![file] ![file] ------------------------------------------------------------------------------------------------------- ![file] ![file] ![file] ![file] , 
 Reference [39] is not applicable and relevant. ![file] ![file] , 
 ![file] Regarding the diameters of the Nono-Particles (NPs), the only place that the authors have indicated the size of NPs is in Figure 7 (X-axis), while there are no information in the entire text to know how or why they have come up with that range of NP sizes! For example, considering the observable trends of curves in Figure 7, what we should expect (regarding the average *Nusselt* number) for particles sizes like 500 (nm) or higher? ![file] , 
 None of the claimed values in Table 3 (also in the text) for **Davis et al.** were found in that reference! ![file] ![file] ![file] ![file] ![file] ![file] ![file] https: pubpeer.com search?q=Chenqi+Fu https: pubpeer.com search?q=Davood+Toghraie ,