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Karyopherin β1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression.
Biomed Pharmacother 2019; 120:109127BP

Abstract

Colorectal cancer (CRC) has become the third most common type of cancer worldwide, and CRC liver metastasis (CRLM) is associated with poor survival rates. However, the molecular mechanisms driving this phenomenon remain unclear. Karyopherin β1 (KPNB1) is an adaptor protein that transports several proteins to the nuclear, and has been reported to play essential role in regulating many cancer-associated pathologies. Nevertheless, its role in CRC is unknown. The study was aimed to explore the role of KPNB1 as a pro-metastatic factor and to reveal the underlying mechanism. Here, the results indicated that KPNB1 expression was markedly increased in CRC samples. KPNB1 expression was gradually up-regulated with CRC development and was tightly correlated with poor prognosis in CRC patients. In vitro results demonstrated that KPNB1 decreasing markedly reduced CRC cell proliferation, migration and invasion, which was positively associated with the expression of MET proto-oncogene (MET). Further analysis revealed that KPNB1 decrease down-regulated the expression of epithelial-mesenchymal transition (EMT)-associated signals. In vivo experiments also demonstrated that KPNB1 knockdown evidently inhibited the tumor growth and metastasis in a CRC xenograft model. Importantly, we found that KPNB1 could interact with MET to modulate cell proliferation and metastasis in CRC. A subsequent mechanistic study illustrated that MET over-expression markedly eliminated KPNB1 silence-inhibited migration and invasion in CRC cells. In summary, KPNB1 deletion repressed the metastasis of CRC cells through interacting with MET, which could be served as a potential prognostic biomarker in CRC patients.

Authors+Show Affiliations

Department of General Surgery Three Wards, Nuclear Industry 215 Hospital of Shaanxi Province, Xianyang, Shaanxi, 712000, China.Department of General Surgery, Hanzhong Central Hospital, NO. 22, Kangfu Road, Hantai District, Hanzhong, Shaanxi, 723000, China. Electronic address: 1919003964@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31629952

Citation

Zhang, Yi, and Ke-Feng Li. "Karyopherin Β1 Deletion Suppresses Tumor Growth and Metastasis in Colorectal Cancer (CRC) By Reducing MET Expression." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 120, 2019, p. 109127.
Zhang Y, Li KF. Karyopherin β1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression. Biomed Pharmacother. 2019;120:109127.
Zhang, Y., & Li, K. F. (2019). Karyopherin β1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 120, p. 109127. doi:10.1016/j.biopha.2019.109127.
Zhang Y, Li KF. Karyopherin Β1 Deletion Suppresses Tumor Growth and Metastasis in Colorectal Cancer (CRC) By Reducing MET Expression. Biomed Pharmacother. 2019;120:109127. PubMed PMID: 31629952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Karyopherin β1 deletion suppresses tumor growth and metastasis in colorectal cancer (CRC) by reducing MET expression. AU - Zhang,Yi, AU - Li,Ke-Feng, Y1 - 2019/10/17/ PY - 2019/04/13/received PY - 2019/06/12/revised PY - 2019/06/12/accepted PY - 2019/10/21/pubmed PY - 2019/10/21/medline PY - 2019/10/21/entrez KW - Colorectal cancer (CRC) KW - KPNB1 KW - MET KW - Metastasis SP - 109127 EP - 109127 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 120 N2 - Colorectal cancer (CRC) has become the third most common type of cancer worldwide, and CRC liver metastasis (CRLM) is associated with poor survival rates. However, the molecular mechanisms driving this phenomenon remain unclear. Karyopherin β1 (KPNB1) is an adaptor protein that transports several proteins to the nuclear, and has been reported to play essential role in regulating many cancer-associated pathologies. Nevertheless, its role in CRC is unknown. The study was aimed to explore the role of KPNB1 as a pro-metastatic factor and to reveal the underlying mechanism. Here, the results indicated that KPNB1 expression was markedly increased in CRC samples. KPNB1 expression was gradually up-regulated with CRC development and was tightly correlated with poor prognosis in CRC patients. In vitro results demonstrated that KPNB1 decreasing markedly reduced CRC cell proliferation, migration and invasion, which was positively associated with the expression of MET proto-oncogene (MET). Further analysis revealed that KPNB1 decrease down-regulated the expression of epithelial-mesenchymal transition (EMT)-associated signals. In vivo experiments also demonstrated that KPNB1 knockdown evidently inhibited the tumor growth and metastasis in a CRC xenograft model. Importantly, we found that KPNB1 could interact with MET to modulate cell proliferation and metastasis in CRC. A subsequent mechanistic study illustrated that MET over-expression markedly eliminated KPNB1 silence-inhibited migration and invasion in CRC cells. In summary, KPNB1 deletion repressed the metastasis of CRC cells through interacting with MET, which could be served as a potential prognostic biomarker in CRC patients. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/31629952/Karyopherin_β1_deletion_suppresses_tumor_growth_and_metastasis_in_colorectal_cancer_(CRC)_by_reducing_MET_expression L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(19)31670-1 DB - PRIME DP - Unbound Medicine ER -