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您的检索式：作者名="Kequan Lin"
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| 1 | Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer显示文摘Metastasis,the development of secondary malignant growths at a distance from a primary tumor,is the cause of death for 90%of cancer patients,but little is known about how metastatic cancer cells adapt to and colonize new tissue environments.Here,using clinical samples,patient-derived xenograft(PDX)samples,PDX cells,and primary/metastatic cell lines,we discovered that liver metastatic colorectal cancer(CRC)cells lose their colon-specific gene transcription program yet gain a liver-specific gene transcription program.We showed that this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical enhancers and super-enhancers.Further,we identified that the liver-specific transcription factors FOXA2 and HNF1A can bind to the gained enhancers and activate the liver-specific gene transcription,thereby driving CRC liver metastasis.Importantly,similar transcription reprogramming can be observed in multiple cancer types.Our data suggest that reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically. | Shuaishuai Teng Yang Eric Li Ming Yang Rui Qi Yiming Huang Qianyu Wang Yanmei Zhang Shanwen Chen Shasha Li Kequan Lin Yang Cao Qunsheng Ji Qingyang Gu Yujing Cheng Zai Chang Wei Guo Pengyuan Wang Ivan Garcia-Bassets Zhi John Lu Dong Wang | 2020 | Cell Research2020，30，1： | 11 |
| 2 | Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun显示文摘Metastasis is the leading cause of human cancer deaths.Unfortunately,no approved drugs are available for antimetastatic treatment.In our study,high-throughput sequencing-based high-throughput screening(HTS^2)and a breast cancer lung metastasis(BCLM)-associated gene signature were combined to discover anti-metastatic drugs.After screening of thousands of compounds,we identified Ponatinib as a BCLM inhibitor.Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models.Mechanistically,Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein.Notably,JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients.Collectively,we established a novel approach for the discovery of anti-metastatic drugs,identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM.Our study may facilitate the therapeutic treatment of BCLM as well as other metastases. | Wei Shao Shasha Li Lu Li Kequan Lin Xinhong Liu Haiyan Wang Huili Wang Dong Wang | 2019 | Protein & Cell2019，10，3： | 7 |
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