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c-Myb promotes growth and metastasis of colorectal cancer through c-fos-induced epithelial-mesenchymal transition.
Qu, Xiao; Yan, Xuebing; Kong, Cheng; Zhu, Yin; Li, Hao; Pan, Dengdeng; Zhang, Xiaohui; Liu, Yongqiang; Yin, Fang; Qin, Huanlong.
Afiliación
  • Qu X; Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
  • Yan X; Shanghai Clinical College, Anhui Medical University, Shanghai, China.
  • Kong C; Institute for Intestinal Diseases, School of Medicine, Tongji University, Shanghai, China.
  • Zhu Y; Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
  • Li H; Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
  • Pan D; Institute for Intestinal Diseases, School of Medicine, Tongji University, Shanghai, China.
  • Zhang X; Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
  • Liu Y; Institute for Intestinal Diseases, School of Medicine, Tongji University, Shanghai, China.
  • Yin F; Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
  • Qin H; Institute for Intestinal Diseases, School of Medicine, Tongji University, Shanghai, China.
Cancer Sci ; 110(10): 3183-3196, 2019 Oct.
Article en En | MEDLINE | ID: mdl-31338937
c-Myb is a crucial transcription factor that participates in various biological functions; however, its role in colorectal cancer (CRC) remains poorly investigated. We first analyzed the expression and clinical significance of c-Myb in a retrospective cohort enrolling 132 CRC patients. Then, the CRISPR/Cas9 technique was used to establish c-Myb gene KO CRC cell lines. Cellular functional assays in vitro and in vivo were used to evaluate the impact of c-Myb KO in CRC cells. Finally, RNA sequencing was used to investigate the potential oncogenic mechanisms regulated by c-Myb in CRC progression and related cellular validations were accordingly carried out. As a result, c-Myb is significantly overexpressed in CRC tissues as compared with adjacent normal tissues. High expression of c-Myb is positively correlated with lymph node metastasis and poor prognosis. Univariate analysis and multivariate analysis further identify c-Myb as an independent unfavorable prognostic factor for CRC patients. c-Myb KO inhibits the proliferation, apoptosis resistance, invasion, metastasis, colony formation and in vivo tumorigenesis of CRC cells. Also, the mechanism investigation indicates that c-Myb may promote CRC progression by regulating c-fos. c-fos overexpression can rescue the inhibitory effect of c-Myb KO on the malignant characteristics of CRC cells. Finally, we find that c-Myb KO inhibits the epithelial-mesenchymal transition (EMT) molecular phenotype in CRC cells, whereas c-fos overexpression can rescue this inhibitory effect. This study suggests that c-Myb promotes the malignant progression of CRC through c-fos-induced EMT and has the potential to be a promising prognostic biomarker and therapeutic target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas Proto-Oncogénicas c-fos / Proteínas Proto-Oncogénicas c-myb Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Sci Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas Proto-Oncogénicas c-fos / Proteínas Proto-Oncogénicas c-myb Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Sci Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido