Chlortetracycline, a Novel Arf Inhibitor That Decreases the Arf6-Dependent Invasive Properties of Breast Cancer Cells

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors:

The manuscript needs some supplements and corrections before it can be considered for acceptance.

There are some notes as follows and also in the attached file with more details (it is not an exhaustive list):

1. As a contributor, should read carefully and strictly refer to the “Instructions to Authors”.
2. In Keywords: A few more keywords should be added to facilitate the article to be found.
3. Please pay attention to the writing of the subtitle in the article.
4. The results description of the article content (lines 117-124) should be correspond to Figure 2A, B, C.
5. It would be better to add a section of “Conclusions and Future Perspectives" in this article.
6. The minor mistakes in lines 4-11, 28, 48, 49, 51, 53, 56, 57, 60, 62, 71, 73, 77, 88, 92, 96, 99, 101-106, 111, 114, 115, 120, 123, 124, 126, 131, 134, 138, 146, 149, 160, 162, 164, 169, 194-196, 199, 203, 215, 218, 221, 227, 229, 237-239, 250, 261, 274, 278, 294, 305, 306, 313, 320, 325, 328, 330, 339, 343-345, 347-353, 357-359, 363, 367, 373, 378, 382, 385-390, 394, 398, 401, 402, 408, 411, 417, 418, 422, 425, 426 (it is not a complete list).
7. References:

The specifications of the references should comply with the “Instructions to Authors”.

For example: Reference 1.

Hashimoto, S., Onodera, Y., Hashimoto, A., Tanaka, M., Hamaguchi, M., Yamada, A., and Sabe, H. (2004) Requirement for Arf6 in breast cancer invasive activities. Proc Natl Acad Sci U S A 101, 6647-6652

Should be modified as,

Hashimoto, S.; Onodera, Y.; Hashimoto, A.; Tanaka, M.; Hamaguchi, M.; Yamada, A.; Sabe, H. Requirement for Arf6 in breast cancer invasive activities. Proc. Natl. Acad. Sci. USA. 2004, 101, 6647-6652.

Comments for author File: Comments.pdf

Author Response

Dear Reviewer

Thank you for your very meticulous correction of our ms.

As you could follow with the "track changes" function in the microsoft word file, we have careful made all the changes you required. We have added new keywords. In the first section of the results we have corrected the text to correspond to the figure 2 (myrArf6 corresponding to panel B and myrArf1 to the C). We have corrected all the typographical errors and the format of the references. However we did not included a full" conclusion" section but instead we have included at the end of the discussion a sentense specifying the future perspectives of our work.

I would like to thank again reviewer#1 of helping us to improve the quality of our manuscript

Reviewer 2 Report

This is a well presented work describing the tumor anti-propagation activity of the FDA approved antibiotic chlortetracycline. The authors present evidence of the CTC-mediated inhibition of the promoted and spontaneous activation of ADP-ribosylation factor 6, a receptor involved in protein maturation and intracellular trafficking which is emerging as a target for the development of anti-tumor drugs. The authors also provide experimental evidence supporting an allosteric inhibition mechanism, the dependence of this process on magnesium, receptor inhibition in vivo, and inhibition of cell migration. No flaws or major issues were detected in the manuscript. 

Minor details to correct:

Line 53: check for the use of the ellipsis

Lines 77, 89, 154, 199, 218, 278, 299: use of italics for words in Latin (Streptomyces, ad hoc, in vitro, in vivo, etc.)

Lines 401 and 402: unusual prefix symbol for concentration and volume units. 

Author Response

I would like to kindly thank the reviewer#2 for his meticulous review of our manuscript and to be supporting.

We have corrected (as seen with the "track changes" function in the microsoft word) all the points raised by reviewer #2