SPDL1 Promotes Lung Metastasis of Triple-Negative Breast Cancer by Targeting the TGF-β/Smad Pathway to Regulate M2 Macrophage Polarization

Breast cancer is a malignant tumor originating from breast epithelial tissue. Globally, there are approximately 2.3 million new breast cancer cases annually, accounting for 11.7% of all new cancer cases. Based on molecular subtype classification, triple-negative breast cancer (TNBC) has a high propensity for lung metastasis and is a major cause of death in breast cancer patients. As key innate immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have a functional status closely related to tumor progression. Recent studies have shown that macrophages in the TME play complex and critical regulatory roles in tumor evolution. Moreover, during the process of TNBC lung metastasis, TAMs are regulated by multiple signaling pathways, thereby driving metastasis. Previous studies have found that the TGF-β/Smad signaling pathway can induce TAM polarization toward the M2 type, which synergistically promotes TNBC lung metastasis. but its mechanism remains unclear. Spindle apparatus coiled-coil protein 1 (SPDL1) plays an important role in regulating cell mitosis and accurate chromosome segregation, and is involved in the occurrence, development, and prognosis evaluation of breast tumors. However, the impact of SPDL1 on the functional status of TAMs and whether the interaction between them is involved in regulating TNBC lung metastasis have not been clearly reported yet. Therefore, this study aims to explore whether SPDL1 affects the process of TNBC lung metastasis by regulating M2 macrophage polarization and clarify its potential molecular mechanism, so as to provide new ideas for the development of novel immune drugs based on SPDL1-macrophages.