Hook1, a microtubule-and cargo-tethering protein, is involved in multiple biological processes. It participates in clathrin-independent endocytosis, sorting cargo proteins like CD98 and CD147 into recycling endosomes [2]. It also plays a role in axonal transport, mediating the transport of TrkB-BDNF-signaling endosomes in primary hippocampal neurons [4].

In cancer research, Hook1 has been shown to have tumor-suppressive functions. In renal cell carcinoma (RCC), Hook1 is downregulated, and its overexpression inhibits tumor growth, metastasis, angiogenesis, and sunitinib resistance through the TGF-β and TNFSF13B/VEGF-A axis [1]. In oesophageal squamous cell carcinoma (ESCC), Hook1 induces necroptosis and inhibits cell proliferation and migration [3]. In hepatocellular carcinoma, Hook1 inhibits malignancy and epithelial-mesenchymal transition, and its downregulation promotes cancer progression [5]. In ovarian cancer, reducing Hook1 levels decreases in vitro growth, migration, and tumor-forming ability in vivo, as well as stem-like capabilities of cancer cells [6]. In the abnormal spermatozoon head shape (azh) mutant mouse, deletion of exons 10 and 11 in the murine Hook1 gene leads to a non-functional protein, causing abnormal sperm head and tail morphology, suggesting a role in spermatogenesis [7].

In conclusion, Hook1 is crucial for normal cellular functions such as endosomal sorting and axonal transport. Its role as a potential tumor suppressor in multiple cancers and its importance in spermatogenesis are significant findings. Research on Hook1, especially through gene knockout or knockdown models, provides insights into biological processes and disease mechanisms, which may contribute to the development of new therapeutic strategies for cancer and male infertility.

References:

1. Yin, Lei, Li, Wenjia, Chen, Xuxiao, Cheng, Bo, Yang, Huan. 2023. HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2206955. doi:10.1002/advs.202206955. https://pubmed.ncbi.nlm.nih.gov/37085921/

2. Higashi, Satoru, Makiyama, Tomohiko, Sakane, Hiroshi, Nogami, Satoru, Shirataki, Hiromichi. 2022. Regulation of Hook1-mediated endosomal sorting of clathrin-independent cargo by γ-taxilin. In Journal of cell science, 135, . doi:10.1242/jcs.258849. https://pubmed.ncbi.nlm.nih.gov/34897470/

3. Cao, Kui, Zhu, Jinhong, Lu, Mengdi, Zhang, Yanqiao, Ma, Jianqun. 2023. Analysis of multiple programmed cell death-related prognostic genes and functional validations of necroptosis-associated genes in oesophageal squamous cell carcinoma. In EBioMedicine, 99, 104920. doi:10.1016/j.ebiom.2023.104920. https://pubmed.ncbi.nlm.nih.gov/38101299/

4. Olenick, Mara A, Dominguez, Roberto, Holzbaur, Erika L F. 2018. Dynein activator Hook1 is required for trafficking of BDNF-signaling endosomes in neurons. In The Journal of cell biology, 218, 220-233. doi:10.1083/jcb.201805016. https://pubmed.ncbi.nlm.nih.gov/30373907/

5. Sun, Xu, Zhang, Qi, Chen, Wei, Liang, Ting-Bo, Bai, Xue-Li. . Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 39, 1010428317711098. doi:10.1177/1010428317711098. https://pubmed.ncbi.nlm.nih.gov/28718370/

6. Suárez-Martínez, Elisa, Piersma, Sander R, Pham, Thang V, Jimenez, Connie R, Carnero, Amancio. 2024. Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy. In Journal of experimental & clinical cancer research : CR, 43, 150. doi:10.1186/s13046-024-03071-2. https://pubmed.ncbi.nlm.nih.gov/38807192/

7. Mendoza-Lujambio, Irene, Burfeind, Peter, Dixkens, Christa, Engel, Wolfgang, Neesen, Juergen. . The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse. In Human molecular genetics, 11, 1647-58. doi:. https://pubmed.ncbi.nlm.nih.gov/12075009/