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. 2022 Dec 15;3:44. doi: 10.1186/s43556-022-00099-8

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© The Author(s) 2022

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/.

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Fig. 3 — Notch-mediated paracrine cycle between BLBCC and TAMs. Activated NOTCH1 and NOTCH3 (possibly) upregulate the expression of IL-1β and CCL2 in tumor cells. IL-1β and CCL2 recruit monocytes into the tumor microenvironment to mature into TAMs. TAM-secreted IL-1β and CCL2 recruit more monocytes and TAMs additionally secrete TGFβ-pro. TGFβ-pro is activated by UPA After being TGFβ, it induces Jagged 1 expression in cancer cells through its receptor TGFβR1 in combination with SMAD2/3. Jagged 1 activates NOTCH1 and NOTCH3 (probably), thus upregulating IL-1β and CCL2 expression