TY - JOUR
T1 - MBIP (MAP3K12 binding inhibitory protein) drives NSCLC metastasis by JNK-dependent activation of MMPs
AU - Ochieng, Joshua Kapere
AU - Kundu, Samrat T.
AU - Bajaj, Rakhee
AU - Leticia Rodriguez, B.
AU - Fradette, Jared J.
AU - Gibbons, Don L.
N1 - Funding Information:
Acknowledgements This work was supported by the DoD CDMRP Lung cancer research award W81XWH-12-16294 and NIH/NCIK K08 CA151651. DLG is an R. Lee Clark Fellow of the University of Texas MD Anderson Cancer Center, supported by the Jeane F Shelby Scholarship Fund. The work was also supported by the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program. We would like to thank Dr. Ignacio Wistuba’s lab for technical support, Jared Fredette and Laura Gibson for technical assistance and the UTMDACC Department of Veterinary Medicine Facility.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/10/22
Y1 - 2020/10/22
N2 - Metastasis is the cause for 90% of cancer-related mortalities. Identification of genetic drivers promoting dissemination of tumor cells may provide opportunities for novel therapeutic strategies. We previously reported an in vivo gain-of-function screen that identified ~30 genes with a functional role in metastasis promotion and characterized detailed mechanistic functions of two hits. In this study, we characterized the contribution of one of the identified genes, MBIP (MAP3K12 binding inhibitory protein), towards driving tumor invasion and metastasis. We demonstrate that expression of MBIP significantly enhances the cellular proliferation, migration and invasion of NSCLC cells in vitro and metastasis in vivo. We functionally characterized that MBIP mediates activation of the JNK pathway and induces expression of matrix metalloproteinases (MMPs), which are necessary for the invasive and metastatic phenotype. Our findings establish a novel mechanistic role of MBIP as a driver of NSCLC progression and metastasis.
AB - Metastasis is the cause for 90% of cancer-related mortalities. Identification of genetic drivers promoting dissemination of tumor cells may provide opportunities for novel therapeutic strategies. We previously reported an in vivo gain-of-function screen that identified ~30 genes with a functional role in metastasis promotion and characterized detailed mechanistic functions of two hits. In this study, we characterized the contribution of one of the identified genes, MBIP (MAP3K12 binding inhibitory protein), towards driving tumor invasion and metastasis. We demonstrate that expression of MBIP significantly enhances the cellular proliferation, migration and invasion of NSCLC cells in vitro and metastasis in vivo. We functionally characterized that MBIP mediates activation of the JNK pathway and induces expression of matrix metalloproteinases (MMPs), which are necessary for the invasive and metastatic phenotype. Our findings establish a novel mechanistic role of MBIP as a driver of NSCLC progression and metastasis.
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U2 - 10.1038/s41388-020-01463-0
DO - 10.1038/s41388-020-01463-0
M3 - Article
C2 - 32963352
AN - SCOPUS:85088954683
SN - 0950-9232
VL - 39
SP - 6719
EP - 6732
JO - Oncogene
JF - Oncogene
IS - 43
ER -