IPO4, also known as Importin-4, is a nuclear import receptor belonging to the karyopherin β family. It is responsible for transporting various cargoes into the nucleus, such as histones H3 and H4 for chromatin assembly, and is involved in multiple biological processes like DNA damage response and cell proliferation regulation [4,5,6]. Its transcription is competitively regulated by transcription factors ELK1 and GABP [4].

In multiple cancers, IPO4 has been shown to play a significant role. In glioma, inhibition of IPO4 expression leads to a reduction in glioma cell proliferation, migration, and invasion, suggesting its potential as a therapeutic target [1]. In ovarian cancer, E3 ubiquitin ligase RNF180 interacts with IPO4, promoting its degradation and thus inhibiting the nuclear translocation of SOX2, which suppresses the progression of ovarian cancer [2]. In bladder cancer, IMP2 enhances the mRNA stability of IPO4, leading to cisplatin resistance, indicating IPO4's role in chemoresistance [3]. In gastric cancer, knockdown of IPO4 by siRNA impairs cell proliferation and migration, suggesting it contributes to gastric cancer progression and poor prognosis [5]. In cervical cancer, IPO4 promotes the nuclear translocation of CEBPD, activating PRKDC-mediated DNA damage repair and causing cisplatin resistance [7].

In conclusion, IPO4 is crucial for nuclear import of key proteins and plays important roles in cancer-related biological processes. The functional studies through loss-of-function experiments in cancer cells have revealed its significant impact on cancer progression and chemoresistance, highlighting its potential as a therapeutic target in various cancers.