Research Papers:

Phospholipase Cγ1 links inflammation and tumorigenesis in colitis-associated cancer

Kwang-Il Park, Kwang-Youn Kim, Tae Woo Oh, Du-Seock Kang, Eung-Kyun Kim, Yong Ryoul Yang, Young-Kyo Seo, Jin-Yeul Ma and Pann-Ghill Suh _

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Oncotarget. 2018; 9:5752-5763. https://doi.org/10.18632/oncotarget.23430

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Kwang-Il Park1, Kwang-Youn Kim1, Tae Woo Oh1, Du-Seock Kang2, Eung-Kyun Kim3, Yong Ryoul Yang2, Young-Kyo Seo2, Jin-Yeul Ma1 and Pann-Ghill Suh2

1Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Cheomdan-ro 70, Dong-gu, Daegu 41062, Republic of Korea

2School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), UNIST-gil 50, Ulsan 44919, Republic of Korea

3Gene and Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Yangsan 50612, Republic of Korea

Correspondence to:

Pann-Ghill Suh, email: [email protected]

Keywords: phospholipase C γ1; inflammation; colorectal cancer; intestinal barrier dysfunction; inflammatory bowel disease

Received: June 26, 2017     Accepted: November 29, 2017     Published: December 19, 2017


Colorectal cancer (CRC) is the third diagnosed cancer and the second leading cause of cancer-related deaths in the United States. Colorectal cancer is linked to inflammation and phospholipase Cγ1 (PLCγ1) is associated with tumorigenesis and the development of colorectal cancer; however, evidence of mechanisms connecting them remains unclear. The tight junctions (TJ), as intercellular junctional complexes, have an important role for integrity of the epithelial barrier to regulate the cellular permeability. Here we found that PLCγ1 regulated colitis and tumorigenesis in intestinal epithelial cells (IEC). To induce the colitis-associated cancer (CAC), we used the AOM/DSS model. Mice were sacrificed at 100 days (DSS three cycles) and 120 days (DSS one cycle). In a CAC model, we showed that the deletion of PLCγ1 in IEC decreased the incidence of tumors by enhancing apoptosis and inhibiting proliferation during tumor development. Accordingly, the deletion of PLCγ1 in IEC reduced colitis-induced epithelial inflammation via inhibition of pro-inflammatory cytokines and mediators. The PLCγ1 pathway in IEC accelerated colitis-induced epithelial damage via regulation of TJ proteins. Conclusions: Our findings suggest that PLCγ1 is a critical regulator of colitis and colorectal cancer and could further help in the development of therapy for colitis-associated cancer.

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