TACC3: a multi-functional protein promoting cancer cell survival and aggressiveness

ABSTRACT

TACC3 is the most oncogenic member of the transforming acidic coiled-coil domain-containing protein (TACC) family. It is one of the major recruitment factors of distinct multi-protein complexes. TACC3 is localized to spindles, centrosomes, and nucleus, and regulates key oncogenic processes, including cell proliferation, migration, invasion, and stemness. Recently, TACC3 inhibition has been identified as a vulnerability in highly aggressive cancers, such as cancers with centrosome amplification (CA). TACC3 has spatiotemporal functions throughout the cell cycle; therefore, targeting TACC3 causes cell death in mitosis and interphase in cancer cells with CA. In the clinics, TACC3 is highly expressed and associated with worse survival in multiple cancers. Furthermore, TACC3 is a part of one of the most common fusions of FGFR, FGFR3-TACC3 and is important for the oncogenicity of the fusion. A detailed understanding of the regulation of TACC3 expression, its key partners, and molecular functions in cancer cells is vital for uncovering the most vulnerable tumors and maximizing the therapeutic potential of targeting this highly oncogenic protein. In this review, we summarize the established and emerging interactors and spatiotemporal functions of TACC3 in cancer cells, discuss the potential of TACC3 as a biomarker in cancer, and therapeutic potential of its inhibition.

KEYWORDS:

• TACC3
• cancer
• spindle
• centrosome
• nucleus
• therapeutic

Disclosure statement

O. Sahin is the co-founder and manager of OncoCube Therapeutics LLC, and the founder and president of LoxiGen, Inc. O. Sahin is also member of the scientific advisory board (SAB) of A2A Pharmaceuticals, Inc. The other authors declare no potential conflicts of interest.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this review article.

Additional information

Funding

This work is supported in part by National Institutes of Health [NIH, R01CA251374 to O. Sahin].