Fig 2: The alteration of MAL2 in pan-cancers. (A) MAL2 mutation level in The Cancer Genome Atlas (TCGA) database. (B) Putative copy-number alterations from GISTIC. (C) Mutation diagram of MAL2 across protein domains. (D) Heatmap of MAL2 DNA methylation and mRNA expression by the Xena browser.

Fig 3: Patients’ survival depends on MAL2 status (89.59% vs. 71.33% 5 years after diagnosis in low-MAL2 and high-MAL2 groups, respectively; p = 0.0244)

Fig 4: Schematics of some proposed functions of MAL-family proteins in cancer cells. (A) MAL and MYADM levels control membrane condensation that, in turn, regulates the confinement of proteins anchored to the inner leaflet of the lipid bilayer through covalently linked fatty acids alone (for instance, Lck) or combined with prenylation (for instance, Rac), respectively, and probably also of specific membrane receptors. (B) MYADM levels modulate ameboid versus mesenchymal movement by regulating the recruitment of Rac to condensed membranes. (C) MAL2 overexpression modulates endocytosis of MHC-I in breast cancer cells. (D) MAL2 organizes specialized membranes to recruit HER2 in breast cancer cells. (E) MAL2 regulates MAPK ERK1/2 signaling in pancreatic cancer cells. (F) Excess of MALL produces cytokinetic defects that lead to aneuploidy. MALL-overexpressing cells may divide normally or undergo cytokinesis failure, giving rise to a binucleated cell (or, if the two nuclei fuse, to a tetraploid cell). Division of this cell can generate diploid, tetraploid, or aneuploid cells depending on the position of the centrosome in metaphase and the occurrence or not of chromosome missegregation.

Fig 5: Role of MAL2 in FTO‐mediated tumor growth in bladder cancer. (A) Representative photographs of tumors in mice (n = 5 per group) injected with 5637 cells stably transduced with the indicated constructs at day 33. (B) Tumor volumes of the xenografts. (C) Tumor weights at day 33. (D) Ki‐67 immunofluorescence staining of the xenograft tumors. Scale bar: 100 μm. (E) The protein levels of FTO and MAL2 in the xenograft tumors. One‐way ANOVA (C, D) and two‐way ANOVA (B) followed by Bonferroni's post hoc test were used to perform the comparisons. **p < 0.01, ***p < 0.001 compared with Vector+shNC. ###p < 0.001 compared with FTO+shNC