miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts.
miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts.
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DOI：
10.1101/gad.347344.120
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发表时间：
2021-08-01
影响因子：
10.5
通讯作者：
He L
中科院分区：
文献类型：
--
作者：
Xue B;Chuang CH;Prosser HM;Fuziwara CS;Chan C;Sahasrabudhe N;Kühn M;Wu Y;Chen J;Biton A;Chen C;Wilkinson JE;McManus MT;Bradley A;Winslow MM;Su B;He L
In this study, Xue et al. identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. They show that miR-200 regulates the functional interaction between cancer cells and CAFs at least in part by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs, providing new insight into the interaction between cancer cells and CAFs as a mechanism to promote metastatic potential. Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.
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影响因子：
--
作者：
Budczies J;von Winterfeld M;Klauschen F;Bockmayr M;Lennerz JK;Denkert C;Wolf T;Warth A;Dietel M;Anagnostopoulos I;Weichert W;Wittschieber D;Stenzinger A
通讯作者：
Stenzinger A
影响因子：
64.5
作者：
Hu B;Castillo E;Harewood L;Ostano P;Reymond A;Dummer R;Raffoul W;Hoetzenecker W;Hofbauer GF;Dotto GP
通讯作者：
Dotto GP
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
3.3
作者：
Gregory PA;Bracken CP;Smith E;Bert AG;Wright JA;Roslan S;Morris M;Wyatt L;Farshid G;Lim YY;Lindeman GJ;Shannon MF;Drew PA;Khew-Goodall Y;Goodall GJ
通讯作者：
Goodall GJ
影响因子：
8
作者：
Ahirwar DK;Nasser MW;Ouseph MM;Elbaz M;Cuitiño MC;Kladney RD;Varikuti S;Kaul K;Satoskar AR;Ramaswamy B;Zhang X;Ostrowski MC;Leone G;Ganju RK
通讯作者：
Ganju RK