Abstract B084: PLOD2 is essential to functional activation of integrin beta1 for invasion/metastasis of cancer

Abstract

Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in various cancer cells, and its critical role as a stabilizer of ITGB1, enabling ITGB1 to initiate tumor invasion/metastasis, which was demonstrated mainly using SCC cells as a representative example. ITGB1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of SCC tissues from patients corroborated PLOD2 expression associated with ITGB1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of ITGB1 that prominently regulates tumor invasion and metastasis not only in SCCs but tumors of diverse origins, and it provides important clues engendering novel therapeutics for these intractable cancers. Citation Format: Eisaku Kondo, Ken Saito. PLOD2 is essential to functional activation of integrin beta1 for invasion/metastasis of cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B084. doi:10.1158/1535-7163.TARG-19-B084