SRC induces podoplanin expression to promote cell migration
Authors: Yongquan Shen
Gary S Goldberg
Chen-Shan Chen
Hitoshi Ichikawa
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: contact normalization; tumor cells; Src; Cas; podoplanin
Affiliations: Molecular Biology Department, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084, USA.

Abstract:  Nontransformed cells can force tumor cells to assume a normal morphology and phenotype by the process of contact normalization. Transformed cells must escape this process to become invasive and malignant. However, mechanisms underlying contact normalization have not been elucidated. Here, we have identified genes that are affected by contact normalization of Src-transformed cells. Tumor cells must migrate to become invasive and malignant. Src must phosphorylate the adaptor protein Cas (Crk-associated substrate) to promote tumor cell motility. We report here that Src utilizes Cas to induce podoplanin (Pdpn) expression to promote tumor cell migration. Pdpn is a membrane-bound extracellular glycoprotein that associates with endogenous ligands to promote tumor cell migration leading to cancer invasion and metastasis. In fact, Pdpn expression accounted for a major part of the increased migration seen in Src-transformed cells. Moreover, nontransformed cells suppressed Pdpn expression in adjacent Src-transformed cells. Of &gt;39,000 genes, Pdpn was one of only 23 genes found to be induced by transforming Src activity and suppressed by contact normalization of Src-transformed cells. In addition, we found 16 genes suppressed by Src and induced by contact normalization. These genes encode growth factor receptors, adaptor proteins, and products that have not yet been annotated and may play important roles in tumor cell growth and migration. 

Retracted: No

PubPeer comments:
 Figure 3C: The number of lanes doesnu2019t seem to match. Is that expected? ![file] , 
 #1 The temperature labelling may be inexact because the experimental conditions were not homogeneous? The graph below shows that a couple of runs had additional or different temperatures, although I haven t tried to verify any detailed correspondence. , 
 This looks like a thermal stability assay which I would assume was done in a gradient thermocycler. Generally the gradient is formed across an 8 strip of samples, so my guess is that the wildtype is perhaps mis-labelled, could be that the first lane is a non-heated samples and the rest match up to the conditions listed for the mutants. , 
 Dear reader, Thank you for bringing these points to our attention. Indeed, there is an unintentional mislabelling in the figure 3C, that however does not affect the results of the study. Our files indicate that the mistake was introduced late in the publishing process. The figure was correct in the original manuscript version that was submitted to the journal for revision. With regard to the R278I mutant profile, the image of the blot misses part of the last (8th) band. We have contacted the journal on this regard. In the meantime, we are posting here a corrected figure 3. Our apologies for the confusion that this may have created and thank you for your attentive reading. ![file] ,