Gene expression profiling of metastatic lung cancer cell lines

During malignant disease progression, the extracellular matrix (ECM) of epithelial tumors accumulates inter-molecular cross-links between collagen strands; these cross-links enhance ECM stiffness and trigger tumor cell invasion and dissemination, but the mechanisms that regulate intra-tumoral collagen maturation have not been fully defined. Using a new mouse model of metastatic lung adenocarcinoma driven by mutant K-ras expression and Cdkn1a inactivation, we showed that tumor cell invasion and metastasis are driven by high expression of lysyl hydroxylase 2 (LH2), an enzyme that hydroxylates telomeric lysine (Lys) residues on collagen.

12

Chen Y, Terajima M, Yang Y, Sun L, Ahn YH, Pankova D, Puperi DS, Watanabe T, Kim MP, Blackmon SH, Rodriguez J, Liu H, Behrens C, Wistuba II, Minelli R, Scott KL, Sanchez-Adams J, Guilak F, Pati D, Thilaganathan N, Burns AR, Creighton CJ, Martinez ED, Zal T, Grande-Allen KJ, Yamauchi M, Kurie JM