Highly Expressed Integrin-α8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse

Abstract

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-α8 (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-α8 is largely unknown. We functionally overexpressed integrin-α8 in MM cell lines, and surprisingly, stemness features including HIF1α, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-α8 expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-α8, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition

“…Meanwhile, the phosphorylation of ERK1/2 was augmented compared to the control cells. A number of studies reported that integrins promote cancer metastasis through epithelial-mesenchymal transition (EMT) [48,49], which are in line with our findings. The IHC data revealed no difference in the expression of ITGA2 in primary and tumor tissues with lymph node metastasis.…”

KAT3B-p300 and H3AcK18/H3AcK14 levels are prognostic markers for kidney ccRCC tumor aggressiveness and target of KAT inhibitor CPTH2

“…This result is in agreement with effects in the deregulation of integrins. It is known, in fact, that their up or downregulation [ 35 , 36 ] is responsible to modulate cell invasion and migration in cancer microenvironment. We finally confirmed the inhibitory activity of CPTH2 on the cell invasiveness properties, performing an in vitro wound healing scratch tests.…”

Sex-Specific Transcriptome Differences in Human Adipose Mesenchymal Stem Cells

“…The gene ITGA8 , among other studies, was studied in multiple myeloma cell lines since it was discovered its high expression in patients with early relapse [ 125 ]. The ITGA8 overexpression in this cell model was associated with an induction of stemness features and epithelial-mesenchymal transition-related phenotypes.…”