TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity.

Centrosome amplification (CA) has been observed in various solid tumors and contributes to chromosomal instability (CIN) and poor clinical prognosis in patients with cancer. CA also inhibits cell proliferation by inducing cell-cycle arrest and cell death. However, the mechanism of regulation of centrosome number in cancer cells and its effect on CIN and cell proliferation remains elusive. Here, we report that tuftelin (TUFT1) is a novel centrosomal protein that localizes to the proximal ends of parent centrioles. TUFT1 prevents CA and mitotic spindle multipolarity by suppressing premature polo-like kinase 1 activation. In addition, TUFT1 is phosphorylated by NIMA-related kinase 2 (NEK2), and the phosphorylation status of TUFT1 is essential for coordinating centrosome number and cell proliferation in cervical and breast cancers. Data from clinical breast cancer samples indicate that the combined detection of TUFT1 and NEK2 expression reflects tumor malignancy and patient survival with higher precision. Overall, these results reveal a crucial role of TUFT1 in the regulation of tumor progression through centrosome number control. Thus, TUFT1 represents a promising target for diagnostic and therapeutic approaches for cancers.