Golph3-KO Mouse

GOLPH3, short for Golgi phosphoprotein 3, is a peripheral membrane protein. It binds specifically to phosphatidylinositol(4)phosphate [PtdIns(4)P] at the Golgi, forming a complex with myosin18A (MYO18A) which binds F-actin. This complex is crucial for vesicle trafficking from the Golgi to the plasma membrane. GOLPH3 is also involved in maintaining Golgi ribbon structure, Golgi glycosylation, and mitochondrial cardiolipin production. It has been linked to the DNA damage response signalling pathway [1,2,3,4,5,6].

The gene encoding GOLPH3 is often amplified in different solid tumours such as melanoma, lung, breast, glioma, and colorectal cancer. Overexpression of GOLPH3 is associated with poor prognosis in multiple tumour types. In Drosophila, RNAi-mediated knockdown of dGOLPH3 reduces wing and eye size, indicating its role in organ growth. Also, in colorectal cancer cells, knockdown of GOLPH3 potentiates ferroptosis, suggesting it as a negative regulator of ferroptosis [3,7,8].

In conclusion, GOLPH3 is essential for multiple cellular functions including vesicle trafficking, Golgi-related processes, and organ growth. Its dysregulation is strongly associated with cancer, and studies using genetic models like RNAi in Drosophila and knockdown in cancer cell lines have revealed its role in tumorigenesis and other disease-related processes such as ferroptosis in colorectal cancer.

References:

1. Kuna, Ramya S, Field, Seth J. 2018. GOLPH3: a Golgi phosphatidylinositol(4)phosphate effector that directs vesicle trafficking and drives cancer. In Journal of lipid research, 60, 269-275. doi:10.1194/jlr.R088328. https://pubmed.ncbi.nlm.nih.gov/30266835/

2. Rizzo, Riccardo, Parashuraman, Seetharaman, D'Angelo, Giovanni, Luini, Alberto. 2016. GOLPH3 and oncogenesis: What is the molecular link? In Tissue & cell, 49, 170-174. doi:10.1016/j.tice.2016.06.008. https://pubmed.ncbi.nlm.nih.gov/27378035/

3. Sechi, Stefano, Frappaolo, Anna, Karimpour-Ghahnavieh, Angela, Piergentili, Roberto, Giansanti, Maria Grazia. 2020. Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer. In International journal of molecular sciences, 21, . doi:10.3390/ijms21030933. https://pubmed.ncbi.nlm.nih.gov/32023813/

4. Giansanti, Maria Grazia, Piergentili, Roberto. . Linking GOLPH3 and Extracellular Vesicles Content-a Potential New Route in Cancer Physiopathology and a Promising Therapeutic Target is in Sight? In Technology in cancer research & treatment, 21, 15330338221135724. doi:10.1177/15330338221135724. https://pubmed.ncbi.nlm.nih.gov/36320176/

5. Frappaolo, Anna, Zaccagnini, Gianluca, Giansanti, Maria Grazia. 2025. GOLPH3-mTOR Crosstalk and Glycosylation: A Molecular Driver of Cancer Progression. In Cells, 14, . doi:10.3390/cells14060439. https://pubmed.ncbi.nlm.nih.gov/40136688/

6. Buschman, Matthew D, Xing, Mengke, Field, Seth J. 2015. The GOLPH3 pathway regulates Golgi shape and function and is activated by DNA damage. In Frontiers in neuroscience, 9, 362. doi:10.3389/fnins.2015.00362. https://pubmed.ncbi.nlm.nih.gov/26500484/

7. Frappaolo, Anna, Karimpour-Ghahnavieh, Angela, Cesare, Giuliana, Vaccari, Thomas, Giansanti, Maria Grazia. 2022. GOLPH3 protein controls organ growth by interacting with TOR signaling proteins in Drosophila. In Cell death & disease, 13, 1003. doi:10.1038/s41419-022-05438-9. https://pubmed.ncbi.nlm.nih.gov/36435842/

8. Chen, Lihua, Wang, Chunxiao, Chen, Xiaojing, Deng, Xian, Qiu, Chengzhi. 2024. GOLPH3 inhibits erastin-induced ferroptosis in colorectal cancer cells. In Cell biology international, 48, 1198-1211. doi:10.1002/cbin.12190. https://pubmed.ncbi.nlm.nih.gov/38825780/