Androgen receptor trafficking via microtubule network (AR-MT trafficking)

Androgen receptor (AR) trafficking via the microtubule network is a critical intracellular process required for the genomic activity of the AR in prostate cancer cells. Upon ligand binding, the AR associates with the dynein motor protein complex and is transported along microtubule tracks from the cytoplasm to the nucleus (Darshan et al., 2011). This translocation is essential for the AR to act as a transcription factor and drive the expression of genes involved in tumor cell proliferation and survival. In the clinical setting, this trafficking pathway is a primary target of taxane-based chemotherapies like docetaxel and cabazitaxel. These agents stabilize microtubules, thereby inhibiting the dynamic reorganization necessary for AR transport and effectively sequestering the receptor in the cytoplasm (Thadani-Mulero et al., 2012). Disruption of this pathway is a key mechanism by which taxanes improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, the emergence of AR splice variants, such as AR-V7, which can translocate to the nucleus independently of microtubules, represents a significant mechanism of therapeutic resistance (Martin et al., 2015).

Other names

Androgen receptor nuclear translocationMicrotubule-mediated AR transportAR-dynein-microtubule axis

Taxanes stabilize microtubules, which prevents the dynamic movement of the dynein-AR complex along the microtubule tracks, thereby sequestering the androgen receptor in the cytoplasm and preventing its nuclear entry and transcriptional activity (Darshan et al., 2011; Thadani-Mulero et al., 2012).