Prefoldin (PFDN) is a co-chaperone protein that is primarily known for its classic cytoplasmic functions in the folding of actin and tubulin monomers during cytoskeletal assembly. Here, we report a marked increase in prefoldin subunit 1 (PFDN1) levels during the transforming growth factor (TGF)-β1-mediated epithelial-mesenchymal transition (EMT) and in human lung tumor tissues. Interestingly, the nuclear localization of PFDN1 was also detected. These observations suggest that PFDN1 may be essential for important novel functions. Overexpression of PFDN1 induced EMT and cell invasion. In sharp contrast, knockdown of PFDN1 generated the opposite effects. Overexpression of PFDN1 was also found to induce lung tumor growth and metastasis. Further experiments showed that PFDN1 overexpression inhibits the expression of cyclin A. PFDN1 suppressed cyclin A expression by directly interacting with the cyclin A promoter at the transcriptional start site. Strikingly, cyclin A overexpression abolished the above PFDN1-mediated effects on the behavior of lung cancer cells, whereas cyclin A knockdown alone induced EMT and increased cell migration and invasion ability. This study reveals that the TGF-β1/PFDN1/cyclin A axis is essential for EMT induction and metastasis of lung cancer cells.

Dear Dr. SchriddeWe would like to thank the Editorial team at Neuron for con nuing to assist us in pilo ng NEURON-D--R through the review process with a "minor revision" decision.We were happy to note that reviewer stated that "This already strong paper is much improved", expressing that "I do not want to stand in the way of the dissemina on of this important work". They suggested a new regression model, although they "realized this is a lot to ask". We have nevertheless implemented this to allay their remaining concerns. Reviewer is fully sa sfied with our work, and in the previous round remarked that "This is an outstanding work -both in terms of the techniques combina on and their applica on in alerts monkeys, the high quality data obtained from several visual areas and the important ques ons".It was heartening to see that reviewer recognized that "The work they report is a tour-de-force of several state-of-the-art methods, and I am sure the results will be very useful to anybody inves ga ng the cor cal representa on of color". Of concern to us however, the third referee now provides a novel set of more extensive, purportedly 'fault-finding' commentary. Much of this could and should have been raised in the first review. Several points betray selec ve reading of the manuscript, and are refuted simply by ci ng the exis ng text (and/or exis ng literature). The first round of review judged the logic of our study as predicated on the assump on that color and form are separately encoded in V . We were obliged to add Figure S in the last revision to address this misconcep on. However, the follow-up review gave no jus fica on for this major cri cism. The second round focused on the broad nature of color processing, yet appear agnos c to the unique value of the current study comparing across three successive visual areas of the same prepara on (a point borne out by the strong support obtained from Reviewers and ). We have nonetheless taken all ac onable sugges ons construc vely (for example, adding a new CIELAB analysis into Figures CD and B), and ensured that we carefully disambiguate any text where improvements can be made (please see our reply to the Reviewers appended to this le er).We would like to re-emphasize that we believe there is no precedent in the literature for such a thorough inves ga on of cor cal func onal organiza on along the visual hierarchy of V , V , and V for color representa on. The color vision system progressively removes the V color bias along the visual pathway and achieves spectral uniformity be er reflec ng color percep on. We have implemented whatever improvements we can, to meet the reviews' expecta on for publica on of this manuscript. We would also like to thank you very much for your me and support and are looking forward to hearing from you.