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S100P contributes to promoter demethylation and transcriptional activation of SLC2A5 to promote metastasis in colorectal cancer.
Lin, Mingdao; Fang, Yuan; Li, Zhenkang; Li, Yongsheng; Feng, Xiaochuang; Zhan, Yizhi; Xie, Yuwen; Liu, Yuechen; Liu, Zehao; Li, Guoxin; Shen, Zhiyong; Deng, Haijun.
Afiliación
  • Lin M; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Fang Y; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Li Z; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Li Y; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Feng X; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Zhan Y; Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Xie Y; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Liu Y; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Liu Z; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
  • Li G; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. gzliguoxin@163.com.
  • Shen Z; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. szy2728@163.com.
  • Deng H; Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. navyd999@163.com.
Br J Cancer ; 125(5): 734-747, 2021 08.
Article en En | MEDLINE | ID: mdl-34188196
BACKGROUND: SLC2A5 is a high-affinity fructose transporter, which is frequently upregulated in multiple human malignant tumours. However, the function and molecular mechanism of SLC2A5 in colorectal cancer (CRC) remain unknown. METHODS: We detected the expression levels of SLC2A5 in CRC tissues and CRC cell lines by western blotting, qRT-PCR and immunohistochemistry. CRC cell lines with stable overexpression or knockdown of SLC2A5 were constructed to evaluate the functional roles of SLC2A5 in vitro through conventional assays. An intrasplenic inoculation model was established in mice to investigate the effect of SLC2A5 in promoting metastasis in vivo. Methylation mass spectrometry sequencing, methylation specific PCR, bisulphite sequencing PCR, ChIP-qPCR and luciferase reporter assay were performed to investigate the molecular mechanism underlying transcriptional activation of SLC2A5. RESULTS: We found that SLC2A5 was upregulated in colorectal tumour tissues. Functionally, a high level of SLC2A5 expression was associated with increased invasion and metastasis capacities of CRC cells both in vitro and in vivo. Mechanistically, we unveiled that S100P could integrate to a specific region of SLC2A5 promoter, thereby reducing its methylation levels and activating SLC2A5 transcription. CONCLUSIONS: Our results reveal a novel mechanism that S100P mediates the promoter demethylation and transcription activation of SLC2A5, thereby promoting the metastasis of CRC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Neoplasias Colorrectales / Regulación hacia Arriba / Metilación de ADN / Transportador de Glucosa de Tipo 5 / Proteínas de Neoplasias Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Br J Cancer Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Neoplasias Colorrectales / Regulación hacia Arriba / Metilación de ADN / Transportador de Glucosa de Tipo 5 / Proteínas de Neoplasias Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Br J Cancer Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido