PBX1-mediated transcription of AP1M2 promotes triple-negative breast cancer malignant progression and docetaxel resistance.

BACKGROUND

Adaptor-related protein complex 1 subunit mu 2 (AP1M2) has been has been shown to be overexpressed in breast cancer tissues. However, whether AP1M2 regulates triple-negative breast cancer (TNBC) progression and chemoresistance is unknown.

METHODS

The expression of AP1M2 and pre-B-cell leukaemia homeobox 1 (PBX1) was analyzed by qRT-PCR or western blot. Cell proliferation, migration, invasion, docetaxel resistance, and apoptosis were analyzed using CCK8 assay, colony formation assay, EdU assay, transwell assay, wound healing assay and flow cytometry. Dual-luciferase reporter assay was used to assess the interaction between AP1M2 and PBX1.

RESULTS

AP1M2 had increased expression in TNBC cells, and its knockdown suppressed TNBC cell proliferation, migration, invasion, and enhanced docetaxel sensitivity. In terms of mechanism, PBX1 bound to AP1M2 promoter region to enhance its transcription. The rescue experiments revealed that overexpression of AP1M2 could abolish the suppressive effect of PBX1 knockdown on TNBC cell proliferation, migration, invasion, and docetaxel resistance.

CONCLUSION

PBX1-mediated AP1M2 facilitates cell proliferation, migration, invasion, and docetaxel resistance to accelerate TNBC malignant behavior, providing a novel target for TNBC treatment.