GNG2, also known as G-protein gamma subunit 2, is a component of the heterotrimeric G protein. It is involved in several cell signaling pathways, such as the PI3K-Akt signaling pathway, and is essential for cell proliferation, angiogenesis, and cell-cycle regulation [1,3]. Genetic models are valuable for studying its functions.

In breast cancer, GNG2 acts as a tumor suppressor. Over-expression of GNG2 blocks the cell cycle, inhibits proliferation, and promotes apoptosis in breast cancer cells in vitro and in vivo. It inhibits the activity of ERK and Akt in an MRAS-dependent manner [1]. In malignant melanoma, GNG2 over-expression inhibits cell metastasis with decreased focal adhesion kinase (FAK) activity, and knockdown of GNG2 enhances migration and invasion [2]. In colorectal cancer, GNG2 over-expression induces G0/G1 arrest, inhibits the PI3K/AKT/mTOR axis, and reduces brain metastasis in an orthotopic xenograft model [3].

In conclusion, GNG2 plays crucial roles in regulating cell proliferation, metastasis, and cell-cycle arrest. The use of gene knockout or conditional knockout mouse models in these studies has revealed its significance in cancer-related processes, suggesting that GNG2 could be a potential therapeutic target for breast, melanoma, and colorectal cancers.

References:

1. Zhao, Anjiang, Li, Dan, Mao, Xiongmin, Yang, Gangyi, Li, Ling. 2022. GNG2 acts as a tumor suppressor in breast cancer through stimulating MRAS signaling. In Cell death & disease, 13, 260. doi:10.1038/s41419-022-04690-3. https://pubmed.ncbi.nlm.nih.gov/35322009/

2. Yajima, Ichiro, Kumasaka, Mayuko Y, Yamanoshita, Osamu, Ohgami, Nobutaka, Kato, Masashi. 2014. GNG2 inhibits invasion of human malignant melanoma cells with decreased FAK activity. In American journal of cancer research, 4, 182-8. doi:. https://pubmed.ncbi.nlm.nih.gov/24660107/

3. Luo, Chenhua, Xiao, ZhiMing, Yang, WenLong. 2025. GNG2 inhibits brain metastases from colorectal cancer via PI3K/AKT/mTOR signaling pathway. In Scientific reports, 15, 1787. doi:10.1038/s41598-025-85592-0. https://pubmed.ncbi.nlm.nih.gov/39805936/