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Tumor‐associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2‐type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non‐erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/− mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid‐derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription–quantitative real‐time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA‐MB‐231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA‐MB‐231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic‐nuclear protein isolation experiments and ChIP‐qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2‐type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization. [ABSTRACT FROM AUTHOR]

Protein palmitoylation, in which C16 fatty acid chains are attached to cysteine residues via a reversible thioester linkage, is one of the most common lipid modifications and plays important roles in regulating protein stability, subcellular localization, membrane trafficking, interactions with effector proteins, enzymatic activity, and a variety of other cellular processes. Moreover, the unique reversibility of palmitoylation allows proteins to be rapidly shuttled between biological membranes and cytoplasmic substrates in a process usually controlled by a member of the DHHC family of protein palmitoyl transferases (PATs). Notably, mutations in PATs are closely related to a variety of human diseases, such as cancer, neurological disorders, and immune deficiency conditions. In addition to PATs, intracellular palmitoylation dynamics are also regulated by the interplay between distinct posttranslational modifications, including ubiquitination and phosphorylation. Understanding the specific mechanisms of palmitoylation may reveal novel potential therapeutic targets for many human diseases. [ABSTRACT FROM AUTHOR]