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. 2023 Aug 10;42:203. doi: 10.1186/s13046-023-02785-z

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© The Author(s) 2023

Open Access This 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. 8 — Graphical abstract illustrating the mechanism of mutp53-driven integrin-α5/β1 expression. Mutant p53 (mutp53) proteins induce the transcription of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5). ENTPD5 operates in the endoplasmic reticulum as a UDPase to generate UMP. Subsequently, UMP is exchanged for UDP-glucose, which is required by UDP-glucose:glycoprotein glucosyltransferase (UGGT) to add a single glucose moiety (represented by a red triangle) to unfolded N-glycoproteins, including integrins. The presence of a single, terminal glucose residue enables the interaction with the lectin chaperones calnexin (CANX) and calreticulin (CALR), promoting proper folding. α-glucosidases I and II (GI, GII) trim glucose moieties and, along with UGGT, regulate the entry and exit of integrins from the CANX/CALR cycle. Once correctly folded, the integrins exit the ER and are transported to the cell membrane through the Golgi apparatus. To avoid the accumulation of misfolded proteins, cells employ the endoplasmic reticulum-associated degradation (ERAD) pathway or activate the unfolded protein response (UPR) mechanisms. At the cell membrane, integrin-α5/β1 dimers are activated, adopting an extended conformation, and form clusters to mediate adhesion to fibronectin, a component of the extracellular matrix (ECM). This process promotes cellular migration, invasion, and metastasis. Created with BioRender.com