Tacc3-flox Mouse

Tacc3, a member of the transforming acidic coiled-coil domain-containing protein (TACC) family, is one of the major recruitment factors of distinct multi-protein complexes. It localizes to spindles, centrosomes, and the nucleus, and is crucial for regulating key oncogenic processes like cell proliferation, migration, invasion, and stemness. It also has spatiotemporal functions throughout the cell cycle, and its study in genetic models can help understand its complex roles [1].

In cancer, Tacc3 has been widely studied. High Tacc3 expression is associated with poor prognosis in multiple cancers such as pancreatic cancer [3], lung carcinoma [5]. In breast cancer with centrosome amplification, Tacc3 forms distinct functional interactomes in mitosis and interphase to ensure cancer cell proliferation and survival. In mitosis, it interacts with KIFC1 to cluster extra centrosomes, and in interphase, it interacts with the NuRD complex in the nucleus to inhibit key tumor suppressors. Targeting Tacc3 can lead to mitotic cell death via multipolar spindle formation and G1 arrest and apoptosis [4]. Additionally, in HER2-positive breast cancer, Tacc3 is overexpressed in T-DM1-resistant cells, and its inhibition can restore T-DM1-induced immunogenic cell death and enhance the drug's efficacy [2].

In conclusion, Tacc3 is a multifunctional protein with a significant role in cancer development and progression. Studies, especially those using models to target Tacc3, have revealed its importance in various oncogenic processes. Understanding Tacc3's functions can potentially lead to new therapeutic strategies for treating aggressive cancers.