Rab22a, a member of the proto-oncogene RAS family and the Rab5 subfamily, is a crucial regulator in multiple biological processes [4]. It participates in early endosome formation and endosomal cargo recycling, regulating vesicle trafficking [2,4]. It also plays a role in the endocytic and secretory routes, being involved in immune functions, such as antigen cross-presentation by dendritic cells and the formation of T-cell conjugates [1].

In osteosarcoma, the chromosomal translocation-derived Rab22a-NeoF fusion proteins drive lung metastasis. Rab22a-NeoF1, for example, binds to SmgGDS-607, releasing GTP-bound RhoA to increase RhoA activity and promote metastasis [3]. In addition, in lung adenocarcinoma, Rab22a promotes cell proliferation, migration, and invasion via up-regulating the PI3K/Akt/mTOR signaling pathway [4]. Also, in multiple myeloma, RAB22A is related to exosome secretion, epithelial-mesenchymal transition (EMT), and immune cell infiltration, and its high expression is associated with disease progression and relapse [5].

In conclusion, Rab22a is essential in endosomal cargo recycling, vesicle trafficking, and immune functions. Its role in cancer-related processes, such as metastasis in osteosarcoma and the malignant phenotype of lung adenocarcinoma, as well as in multiple myeloma progression, is significant. The study of Rab22a through various models helps in understanding the mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Mayorga, Luis S, Cebrian, Ignacio. 2018. Rab22a: A novel regulator of immune functions. In Molecular immunology, 113, 87-92. doi:10.1016/j.molimm.2018.03.028. https://pubmed.ncbi.nlm.nih.gov/29631761/

2. Kong, Lingjie, Huang, Shenghao, Bao, Yuxuan, Hua, Chunyan, Gao, Sheng. 2023. Crucial roles of Rab22a in endosomal cargo recycling. In Traffic (Copenhagen, Denmark), 24, 397-412. doi:10.1111/tra.12907. https://pubmed.ncbi.nlm.nih.gov/37340959/

3. Liao, Dan, Zhong, Li, Yin, Junqiang, Chen, Jian, Kang, Tiebang. 2020. Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma. In Nature cell biology, 22, 868-881. doi:10.1038/s41556-020-0522-z. https://pubmed.ncbi.nlm.nih.gov/32483387/

4. Wang, Jinping, Luo, Xue, Lu, Jinxi, Li, Qingchang, Wang, Liang. 2022. Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway. In Experimental cell research, 416, 113179. doi:10.1016/j.yexcr.2022.113179. https://pubmed.ncbi.nlm.nih.gov/35487271/

5. Fan, Bingjie, Wang, Li, Wang, Jishi. 2024. RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma. In Aging, 16, 4169-4190. doi:10.18632/aging.205565. https://pubmed.ncbi.nlm.nih.gov/38431306/