A glycolytic mechanism regulating an angiogenic switch in prostate cancer
Authors: Chuen-Long Wei
Aaron M Havens
Jacques E Nor
Younghun Jung
Russell S Taichman
Jincheng Wang
Yu Wang
Jianhua Wang
Cun-Yu Wang
Kenneth J Pienta
Phillip J Hogg
Jinlu Dai
Evan T Keller
Journal: Cancer Research (2007)
Discipline: CLINICAL MEDICINE
Keywords: angiogenic switch; tumor growth; metastasis; angiogenesis; CXCL12/CXCR4 signaling
Affiliations: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109, USA.

Abstract:  The generation of an "angiogenic switch" is essential for tumor growth, yet its regulation is poorly understood. In this investigation, we explored the linkage between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that CXCR4 regulates the expression and secretion of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 reduced the secretion of vascular endothelial growth factor and interleukin-8 and increased the generation of angiostatin. At metastatic sites, however, high levels of CXCL12 signaling through CXCR4 reduced PGK1 expression, releasing the angiogenic response for metastastic growth. These data suggest that PGK1 is a critical downstream target of the chemokine axis and an important regulator of an "angiogenic switch" that is essential for tumor and metastatic growth. 

Retracted: Yes

PubPeer comments:
 I find quite strange (or even impossible) that the method developed in this paper could give correct results. The approximation is obtained by replacing $f(t,y(t))$ with the interpolant polynomial on $t_{n-1}$ and $t_{n}$. Anyway, this approximation is used on the large interval $[0,t_{n+1}]$ and not just on $[t_{n-1},t_{n}]$. Results on the remainder of polynomial interpolation say that the in this case the remainder is incredibly high: it is indeed proportional to $(t-t_{n})(t-t_{n-1})$ and hence bounded by $t_{n+1}^2$. In my opinion the analysis of convergence in Theorem 3.1 has some flaws. Indeed, the inequality between page 6 and page 7 does not make sense. It seems that it has been obtained by using an inequality as $$ left| prod_{i=0}^2 (t-t_i) right| le h^3 $$ which does not make sense. Maybe a correct inequality could be $$ left| prod_{i=0}^2 (t-t_i) right| le t^3t $$ but in this case the method would diverge. Moreover, I do not think that last equation at page 6 is correct. Instead of the term $$ left| prod_{i=0}^2 (t-t_i) right| $$ it is possible that there should be the term $$ left| prod_{i=n-1}^n (t-t_i) right| $$ although this correction would not show any substantial improvement of the convergence properties of the method (it still remains a non-convergent method). Could the authors provide a clarification of these issues? , 
 #1 I have found some comments related to this paper in the comments section of another paper on ResearchGate. See https: www.researchgate.net publication 326782310_Modeling_and_analysis_of_the_fractional_HBV_model_with_Atangana-Baleanu_derivative comments , 
 A corrigendum to this paper has been published at https: doi.org 10.1051 mmnp 2021039. In this note it is now affirmed that the method is  *very accurate* (but for just one very simple problem) when the fractional order $alpha$ is above 0.75. There is however no proof for this claim and the few numerical experiments which should support the claim are performed just for values of $alpha=0.97$ and $alpha=0.995$, i.e. values very close to $alpha=1$ (the only value for which the method can work). Indeed, this is a local method which cannot work properly for nonlocal problems. Why the authors affirm the accuracy of the method for $alpha 0.75$ and they do not show the results, for instance, when $alpha=0.8$ or $alpha=0.9$? ,