https://scholars.lib.ntu.edu.tw/handle/123456789/557713
Title: | The inhibition of Wnt restrain KRASG12V-driven metastasis in non-small-cell lung cancer | Authors: | Hung P.-S. Huang M.-H. Kuo Y.-Y. CHIH-HSIN YANG |
Keywords: | KRASG12D; KRASG12V; Metastasis; NSCLC; RhoA; Wnt/β-catenin | Issue Date: | 2020 | Publisher: | MDPI AG | Journal Volume: | 12 | Journal Issue: | 4 | Source: | Cancers | Abstract: | The KRAS mutations have been an obstacle to identify therapeutic targets in cancer treatment. In this work, we clarified the distinct metastasis pattern of non-small-cell lung carcinoma (NSCLC) induced by KRASG12V/KRASG12D mutations and inhibited the KRASG12V mediated metastasis by Wnt inhibitor. First, we found that KRASG12V induced more aggressive phenotype in vitro and in vivo experiments. The Gene Set Enrichment Analysis (GSEA) results of H838 KRASG12V cells showed a significant negative correlation with RhoA-related signaling. Following this clue, we observed KRASG12D induced higher activation of RhoA and suppressed activation of Wnt/β-catenin in H838KRASG12D cells. The restored activation of Wnt/β-catenin in H838KRASG12D cells could be detected when expression with a dominant-negative mutant of RhoA or treatment with RhoA inhibitor. Furthermore, the Wnt inhibitor abolished the KRASG12V-induced migration. We elucidated the importance of the axis of RhoA/Wnt in regulatory NSCLC metastasis driven by KRAS mutations. Our data indicate that KRASG12V driven NSCLC metastasis is Wnt-dependent and the mechanisms of NSCLC metastasis induced by KRASG12V/KRASG12D is distinct. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083064539&doi=10.3390%2fcancers12040837&partnerID=40&md5=4022f66a58f92b1eb811376636189dc2 https://scholars.lib.ntu.edu.tw/handle/123456789/557713 |
ISSN: | 2072-6694 | DOI: | 10.3390/cancers12040837 | SDG/Keyword: | beta catenin; K ras protein; lgk 974; nerve cell adhesion molecule; protein inhibitor; RhoA guanine nucleotide binding protein; unclassified drug; uvomorulin; vimentin; Wnt protein; animal experiment; animal model; animal tissue; Article; cell invasion; cell migration; cell proliferation; cell structure; controlled study; down regulation; epithelial mesenchymal transition; gene expression profiling; gene mutation; human; human cell; in vitro study; in vivo study; MAPK signaling; metastasis; mouse; NCI-H838 cell line; non small cell lung cancer; nonhuman; nude mouse; oncogene K ras; phenotype; protein expression; SK-LU-1 cell line; Wnt signaling |
Appears in Collections: | 腫瘤醫學研究所 |
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