Qian Chen1,2, Li Zhong1, Chao Zhou3, Yan Feng1, Quan-Xing Liu4, Dong Zhou4, Xiao Lu4, Guang-Sheng Du3, Dan Jian1, Hao Luo1, Dong Wang1, Hong Zheng5, Yuan Qiu6,7. 1. Cancer Center of Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China. 2. State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, 400037, China. 3. Department of General Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China. 4. Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China. 5. Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China. ziecoe@tmmu.edu.cn. 6. Department of General Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China. xiaoq2037@qq.com. 7. State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University (Army Medical University), Chongqing, 400037, China. xiaoq2037@qq.com.
Abstract
BACKGROUND: Accumulating evidence shows that Parkinson's disease is negatively associated with colon cancer risk, indicating that Parkinson's disease family proteins may be involved in the initiation of colon cancer. Here, we aimed to identify a Parkinson's disease-related gene involved in colon cancer, elucidate the underlying mechanisms, and test whether it can be used as a target for cancer therapy. METHODS: We first screened colon cancer and normal tissues for differential expression of Parkinson's disease-associated genes and identified ATP13A2, which encodes cation-transporting ATPase 13A2, as a putative marker for colon cancer. We next correlated ATP13A2 expression with colon cancer prognosis. We performed a series of ATP13A2 knockdown and overexpression studies in vitro to identify the contribution of ATP13A2 in the stemness and invasive capacity of colon cancer cells. Additionally, autophagy flux assay were determined to explore the mechanism of ATP13A2 induced stemness. Finally, we knocked down ATP13A2 in mice using siRNA to determine whether it can be used as target for colon cancer treatment. RESULTS: Colon cancer patients with high ATP13A2 expression exhibit shorter overall survival than those with low ATP13A2. Functionally, ATP13A2 acts as a novel stimulator of stem-like traits. Furthermore, knockdown of ATP13A2 in HCT116 resulted in decreased levels of cellular autophagy. Additionally, bafilomycin A1, an autophagy inhibitor, reversed the ATP13A2-induced stemness of colon cancer cells. Lastly treatment with ATP13A2 siRNA reduced the volume of colon cancer xenografts in mice. CONCLUSIONS: The PD-associated gene ATP13A2 is involved in colon cancer stemness through regulation of autophagy. Furthermore, ATP13A2 is a novel prognostic biomarker for colon cancer and is a potential target for colon cancer therapy.
BACKGROUND: Accumulating evidence shows that Parkinson's disease is negatively associated with colon cancer risk, indicating that Parkinson's disease family proteins may be involved in the initiation of colon cancer. Here, we aimed to identify a Parkinson's disease-related gene involved in colon cancer, elucidate the underlying mechanisms, and test whether it can be used as a target for cancer therapy. METHODS: We first screened colon cancer and normal tissues for differential expression of Parkinson's disease-associated genes and identified ATP13A2, which encodes cation-transporting ATPase 13A2, as a putative marker for colon cancer. We next correlated ATP13A2 expression with colon cancer prognosis. We performed a series of ATP13A2 knockdown and overexpression studies in vitro to identify the contribution of ATP13A2 in the stemness and invasive capacity of colon cancer cells. Additionally, autophagy flux assay were determined to explore the mechanism of ATP13A2 induced stemness. Finally, we knocked down ATP13A2 in mice using siRNA to determine whether it can be used as target for colon cancer treatment. RESULTS:Colon cancerpatients with high ATP13A2 expression exhibit shorter overall survival than those with low ATP13A2. Functionally, ATP13A2 acts as a novel stimulator of stem-like traits. Furthermore, knockdown of ATP13A2 in HCT116 resulted in decreased levels of cellular autophagy. Additionally, bafilomycin A1, an autophagy inhibitor, reversed the ATP13A2-induced stemness of colon cancer cells. Lastly treatment with ATP13A2 siRNA reduced the volume of colon cancer xenografts in mice. CONCLUSIONS: The PD-associated gene ATP13A2 is involved in colon cancer stemness through regulation of autophagy. Furthermore, ATP13A2 is a novel prognostic biomarker for colon cancer and is a potential target for colon cancer therapy.
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