MACC1, short for Metastasis Associated in Colon Cancer 1, is an oncogene identified in colon cancer and present in over 20 types of solid cancers [1,2,3,6]. It is a key prognostic biomarker and promotes tumor migration, initiation, proliferation, and metastasis. MACC1 transcriptionally regulates genes involved in epithelial-mesenchymal transition (EMT), such as c-MET, and impacts tumor cell migration and invasion [6]. It also has an impact on the immune-modulatory effects and induced therapy resistance [2].

In pancreatic cancer, overexpression or knockdown of MACC1 in PC cells correspondingly promoted or inhibited pancreatic cancer cell migration and invasion in a MET-independent manner. Knockdown of MACC1 in PC cells markedly decreased the liver metastatic lesions in a liver metastasis model. Mechanistically, MACC1 binds to the EMT regulator SNAI1 to drive EMT, leading to pancreatic cancer cell metastasis [7]. In colorectal cancer, curcumin reduced MACC1 expression, restricted MACC1-induced proliferation, and reduced MACC1-induced cell motility [4]. GIPC1, as a protein interaction partner and transcription factor of MACC1, was found to regulate MACC1-driven metastasis. GIPC1 knockdown reduced endogenous MACC1 expression, and diminished MACC1-induced cell migration and invasion, as well as tumor growth and metastasis in mice [5].

In conclusion, MACC1 is a crucial molecule in cancer metastasis, playing important roles in various solid cancers like pancreatic and colorectal cancer. Through model-based research, such as in vivo mouse models, its functions in promoting metastasis and the underlying mechanisms have been revealed. Targeting MACC1 could potentially offer new strategies for cancer treatment and prevention [4,5,7].

References:

1. Lv, Mengmeng, Jiao, Yunjuan, Yang, Bowen, Su, Wei, Zhong, Jiateng. 2023. MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer. In Biology, 12, . doi:10.3390/biology12030455. https://pubmed.ncbi.nlm.nih.gov/36979146/

2. Schöpe, Paul Curtis, Torke, Sebastian, Kobelt, Dennis, Walther, Wolfgang, Stein, Ulrike. 2024. MACC1 revisited - an in-depth review of a master of metastasis. In Biomarker research, 12, 146. doi:10.1186/s40364-024-00689-4. https://pubmed.ncbi.nlm.nih.gov/39580452/

3. Stein, Ulrike, Dahlmann, Mathias, Walther, Wolfgang. 2009. MACC1 - more than metastasis? Facts and predictions about a novel gene. In Journal of molecular medicine (Berlin, Germany), 88, 11-8. doi:10.1007/s00109-009-0537-1. https://pubmed.ncbi.nlm.nih.gov/19787327/

4. Güllü, Nazli, Smith, Janice, Herrmann, Pia, Stein, Ulrike. 2022. MACC1-Dependent Antitumor Effect of Curcumin in Colorectal Cancer. In Nutrients, 14, . doi:10.3390/nu14224792. https://pubmed.ncbi.nlm.nih.gov/36432477/

5. Siegel, Franziska, Schmidt, Hannes, Juneja, Manisha, Schlag, Peter M, Stein, Ulrike. 2023. GIPC1 regulates MACC1-driven metastasis. In Frontiers in oncology, 13, 1280977. doi:10.3389/fonc.2023.1280977. https://pubmed.ncbi.nlm.nih.gov/38144523/

6. Radhakrishnan, Harikrishnan, Walther, Wolfgang, Zincke, Fabian, Dahlmann, Mathias, Stein, Ulrike. . MACC1-the first decade of a key metastasis molecule from gene discovery to clinical translation. In Cancer metastasis reviews, 37, 805-820. doi:10.1007/s10555-018-9771-8. https://pubmed.ncbi.nlm.nih.gov/30607625/

7. Zhang, Xianglian, Luo, Ya, Cen, Yu, Yang, Shiming, Qin, Shanyu. 2022. MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1. In Cell death & disease, 13, 923. doi:10.1038/s41419-022-05285-8. https://pubmed.ncbi.nlm.nih.gov/36333284/