Invasive
cancer growth and
metastasis account for the poor prognosis of high-grade
breast cancer. Recently, we reported that kinectin 1 (KTN1), a member of the
kinesin-
binding protein family, promotes cell invasion of
triple-negative breast cancer and high-grade
breast cancer cells by augmenting the NF-κB signaling pathway. However, the upstream mechanism regulating KTN1 is unknown. Therefore, this functional study was performed to decipher the regulatory cohort of KTN1 in high-grade
breast cancer. Bioinformatic analysis indicated that
transcription factor Yin Yang 1 (YY1) was a potential
transactivator of KTN1. High YY1 expression correlated positively with pathological progression and poor prognosis of high-grade
breast cancer. Additionally, YY1 promoted cell invasive growth both in vitro and in vivo, in a KTN1-dependent manner. Mechanistically, YY1 could transactivate the KTN1 gene promoter. Alternatively, YY1 could directly interact with a co-factor, DEAD-box helicase 3 X-linked (DDX3X), which significantly co-activated YY1-mediated transcriptional expression of KTN1. Moreover, DDX3X augmented YY1-KTN1 signaling-promoted invasive cell growth of
breast cancer. Importantly, overexpression of YY1 enhanced
tumor aggressive growth in a mouse
breast cancer model. Our findings established a novel DDX3X-assisted YY1-KTN1 regulatory axis in
breast cancer progression, which could lead to the development novel therapeutic targets for
breast cancer.