The upregulated MALAT1 enhances the binding between USP8 and N-HER2, inhibiting the N-HER2 ubiquitin proteasomal degradation and promoting N-HER2 accumulation, PAK5 induces HER2 accumulation by inhibiting N-HER2 ubiquitination degradation via stabilization of MALAT1, which occurs through PAK5-mediated phosphorylation of METTL14, thereby playing a crucial role in breast cancer targeted trastuzumab resistance. Here, METTL14 is linked to breast cancer.