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. 2020 Mar 14;13:19. doi: 10.1186/s13045-020-00858-6

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Complex mechanisms and signaling pathways underlying VM formation. (1) Hypoxia is one of the major important factors in VM formation and contributes to several crucial pathways by regulating expression of some signaling molecules, the expression of HIF-α is positively correlated with hypoxia target genes such as Twist, VEGF, and VEGFR. (2) lncRNA MALAT1 regulates VM formation via VE-cadherin, FAK/ERK signaling pathway, miR-27b and miR-27a-3p target VE-cadherin to regulate VM formation. (3) PI3K, AKT, and PKA are involved in the process of VM formation by PKA/MEK/ERK and TGF-β/PI3K/AKT axis. (4) Notch pathway mediates VM formation through the activation of Ras.