Rab14, a member of the small GTPase RAB family, localizes at the endoplasmic reticulum, Golgi apparatus, and endosomal compartments. It acts as a molecular switch, cycling between a GDP-bound inactive state and a GTP-bound active state, regulating vesicle circulation between the Golgi and endosomal compartments [2]. It is involved in multiple biological processes, such as autophagy, epithelial-mesenchymal transition (EMT), and cytokinesis, and is associated with pathways like the PI3K/AKT signaling pathway [1,4].

Depletion of Rab14 in various cell models has revealed its crucial roles. In mouse oocytes, Rab14 siRNA injection led to large polar bodies, spindle migration defects, and aberrant Golgi apparatus distribution, suggesting its importance in actin-based asymmetric division [2]. In bladder cancer cells, knocking down RAB14 inhibited EMT, autophagy, cell migration, invasion, and proliferation, and induced apoptosis. It was also found that RAB14-promoted EMT and invasion could be reversed by an autophagy activator, indicating its role in the autophagy-dependent AKT signaling pathway in bladder cancer [1]. In pancreatic cancer, Rab14 siRNA knockdown inhibited cell proliferation, colony formation, and invasion, and increased gemcitabine sensitivity [3].

In conclusion, Rab14 is essential for multiple cellular processes and is closely associated with cancer-related phenotypes. Loss-of-function studies, such as those using siRNA to knock down Rab14 in various cell models, have provided insights into its role in processes like asymmetric cell division, autophagy, and EMT, and its implications in cancer development and treatment response.

References:

1. Deng, Huanhuan, Deng, Leihong, Chao, Haichao, Peng, Lifen, Zeng, Tao. 2023. RAB14 promotes epithelial-mesenchymal transition in bladder cancer through autophagy‑dependent AKT signaling pathway. In Cell death discovery, 9, 292. doi:10.1038/s41420-023-01579-8. https://pubmed.ncbi.nlm.nih.gov/37558664/

2. Zou, Yuan-Jing, Shan, Meng-Meng, Wang, Hong-Hui, Ju, Jia-Qian, Sun, Shao-Chen. 2021. RAB14 GTPase is essential for actin-based asymmetric division during mouse oocyte maturation. In Cell proliferation, 54, e13104. doi:10.1111/cpr.13104. https://pubmed.ncbi.nlm.nih.gov/34323331/

3. Ge, Jinnian, Ge, Chunlin. 2018. Rab14 overexpression regulates gemcitabine sensitivity through regulation of Bcl-2 and mitochondrial function in pancreatic cancer. In Virchows Archiv : an international journal of pathology, 474, 59-69. doi:10.1007/s00428-018-2455-5. https://pubmed.ncbi.nlm.nih.gov/30267303/

4. Ge, Pupu, Lei, Zehui, Yu, Yang, Liu, Cui Hua, Wang, Jing. 2021. M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival. In Autophagy, 18, 576-594. doi:10.1080/15548627.2021.1938912. https://pubmed.ncbi.nlm.nih.gov/34092182/