Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases

Joechle K, Jumaa H, Thriene K, Hellerbrand C, Kulemann B, Fichtner-Feigl S, Lang SA, Guenzle J (2022)


Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 9

Article Number: 785979

DOI: 10.3389/fcell.2021.785979

Abstract

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027—a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

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APA:

Joechle, K., Jumaa, H., Thriene, K., Hellerbrand, C., Kulemann, B., Fichtner-Feigl, S.,... Guenzle, J. (2022). Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases. Frontiers in Cell and Developmental Biology, 9. https://doi.org/10.3389/fcell.2021.785979

MLA:

Joechle, Katharina, et al. "Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases." Frontiers in Cell and Developmental Biology 9 (2022).

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