MYBBP1A是一个受机械调节的系统的组成部分，通过调控黏着斑改变乳腺癌转移潜能

MYB binding protein 1a (MYBBP1A) was first identified for its ability to bind and repress the proto-oncogene c-MYB. Most research focuses on its role in regulating ribosomal RNA (rRNA) transcription; However, its impact on metastasis remains unclear. Analysis of TCGA breast cancer patient data reveals higher MYBBP1A levels are associated with shorter survival times in breast cancer patients, while a Mybbp1a knockdown (KD) gene signature, generated by machine learning, indicates significantly improved patient survival outcomes. Using mouse spontaneous metastasis model, we confirmed that MYBBP1A loss suppresses breast cancer cell metastasis. Further analysis revealed that Mybbp1a KD cells exhibit robust abnormalities in cell morphology, which is associated with reduced cell invasion and disrupted F-actin organization. Cell morphological changes are partially rescued in type I collagen-coated high stiffness extracellular matrix (ECM) culture, indicating MYBBP1A could be part of a mechanically modulated system that alters breast cancer metastatic potential. This is supported by the observation that MYBBP1A levels exhibit a gradually increase in response to the increases of ECM stiffness, which is coupled with increased cell invasion capacity. Mechanical stimuli from the tumor microenvironment play an important role in mediating breast cancer metastasis. The pathways that cancer cells use to sense and leverage mechanical cues are largely driven by the assembly and disassembly of focal adhesions, which regulate the dynamics of F-actin stress fibers and couple F-actin with the extracellular matrix (ECM) to transduce mechano-signaling to nucleus and regulate cell motility. Focal adhesion can be visualized by immunofluorescence (IF) staining of phospho-FAK (focal adhesion kinase) plaques at the points of F-actin filaments and be measured by FAK level. Our data shows focal adhesion is reduced in Mybbp1a KD cells, evidenced by weakened level and number of phospho-FAK clustering at the points of F-actin. In parallel, overexpression of FAK rescues breast cancer cell phenotypes and partially restores the reduced cell metastasis capacity observed in Mybbp1a KD. In exploring the function of MYBBP1A in regulating mechanosignal transduction, we found that SUN2, an important component of the Linker of Nucleoskeleton to the Cytoskeleton (LINC) complex, was stripped from nuclear envelop and relocated to heterochromatin dense areas, upon Mybbp1a KD. That breaks the connection between nucleus and cytoskeleton and could explain the reduced focal adhesion assembly following Mybbp1a KD. In the future, we will keep studyingFuture work will focus on the role of MYBBP1A as part of a mechanically modulated complex that is important in promoting breast cancer metastasis.