Rab11a, also known as Ras-related protein in brain 11A, is a small GTPase that serves as a key regulator in vesicle trafficking, a cellular process crucial for material transport and information delivery [1]. It is involved in multiple pathways, such as endocytic recycling regulation, receptors and adhesion molecules recycling, exosome secretion, phagophore formation, cytokinesis, and Hippo-YAP signaling pathway [1,8].

In cancer research, Rab11a shows dual characteristics. In gastric, ovarian, prostate, and lung squamous cell carcinomas, its overexpression promotes cell proliferation, invasion, and resistance to drugs like cisplatin, often via the FAK/AKT or FGFR-signaling pathways [3,4,5,7]. For example, in gastric cancer, its up-regulation facilitates cell growth and invasion through the FAK/AKT pathway [3]. In ovarian cancer, it promotes malignancy by inducing autophagy [4]. In prostate cancer, it activates the FAK/AKT pathway to promote cell malignant progression [5]. In lung squamous cell carcinoma, it is associated with cancer aggressiveness through regulation of FGFR-signaling [7]. Also, in colorectal cancer, stress-induced Rab11a-exosomes can induce amphiregulin-mediated cetuximab resistance [2]. In intestinal epithelial progenitor cells, Rab11a along with Rab11b controls mitotic spindle function, as compound ablation in mice leads to defective cell cycle entry, mitotic arrest, and apoptosis [6].

In summary, Rab11a plays essential roles in multiple biological processes, especially in vesicle-related functions. Its dysregulation is associated with various cancers, and studies using gene-knockout or conditional-knockout mouse models have revealed its significant impact on cancer progression and cell cycle regulation in intestinal tissues, providing valuable insights into potential therapeutic strategies for these diseases.

References:

1. Guo, Rui-Jian, Cao, Yu-Fei, Li, En-Min, Xu, Li-Yan. 2023. Multiple functions and dual characteristics of RAB11A in cancers. In Biochimica et biophysica acta. Reviews on cancer, 1878, 188966. doi:10.1016/j.bbcan.2023.188966. https://pubmed.ncbi.nlm.nih.gov/37657681/

2. Mason, John D, Marks, Ewan, Fan, Shih-Jung, Cunningham, Chris, Goberdhan, Deborah C I. . Stress-induced Rab11a-exosomes induce amphiregulin-mediated cetuximab resistance in colorectal cancer. In Journal of extracellular vesicles, 13, e12465. doi:10.1002/jev2.12465. https://pubmed.ncbi.nlm.nih.gov/38887984/

3. Du, Jiang, Fu, Lin, Hao, Jie, Lin, Xiumin, Dong, Qianze. 2020. Rab11a Is Overexpressed in Gastric Cancer and Regulates FAK/AKT Signaling. In Journal of oncology, 2020, 3494396. doi:10.1155/2020/3494396. https://pubmed.ncbi.nlm.nih.gov/33178272/

4. Wang, Yazhuo, Ren, Yanan, Li, Na, Zhao, Jing, Zhao, Sufen. 2022. Rab11a promotes the malignant progression of ovarian cancer by inducing autophagy. In Genes & genomics, 44, 1375-1384. doi:10.1007/s13258-022-01314-0. https://pubmed.ncbi.nlm.nih.gov/36125654/

5. Chen, Weifang, Wang, Junjun. 2023. RAB11A Promotes Cell Malignant Progression and Tumor Formation of Prostate Cancer via Activating FAK/AKT Signaling Pathway. In Evidence-based complementary and alternative medicine : eCAM, 2023, 5885387. doi:10.1155/2023/5885387. https://pubmed.ncbi.nlm.nih.gov/36760469/

6. Joseph, Ivor, Flores, Juan, Farrell, Victoria, Goldenring, James R, Gao, Nan. 2023. RAB11A and RAB11B control mitotic spindle function in intestinal epithelial progenitor cells. In EMBO reports, 24, e56240. doi:10.15252/embr.202256240. https://pubmed.ncbi.nlm.nih.gov/37424454/

7. Gombodorj, Navchaa, Azuma, Yoko, Yokobori, Takehiko, Saeki, Hiroshi, Shirabe, Ken. 2022. RAB11A Expression Is Associated With Cancer Aggressiveness Through Regulation of FGFR-Signaling in Lung Squamous Cell Carcinoma. In Annals of surgical oncology, 29, 7149-7162. doi:10.1245/s10434-022-11833-5. https://pubmed.ncbi.nlm.nih.gov/35644860/

8. Goswami, Sayantani, Balasubramanian, Iyshwarya, D'Agostino, Luca, Bonder, Edward M, Gao, Nan. 2021. RAB11A-mediated YAP localization to adherens and tight junctions is essential for colonic epithelial integrity. In The Journal of biological chemistry, 297, 100848. doi:10.1016/j.jbc.2021.100848. https://pubmed.ncbi.nlm.nih.gov/34058200/