Proteolytic processing of laminin and the role of cryptides in tumoral biology

Remodelamento da matriz extracelular e mecanismos de resposta ao estresse induzidos pelo peptídeo da laminina C16 em células expostas à hipóxia química ou baixa tensão de oxigênio.

“…Thus, as for the IKVAV (or SIKVAV), from the α1 chain, the induction of adhesion, migration, tumor growth, angiogenesis and metastasis were observed (Tashiro et al, 1989;Kanemoto et al, 1990;Grant et al, 1992;Nomizu et al, 1992). Moreover, studies from our group demonstrated that IKVAV plays a role in MMPs secretion, which was regulated by integrins mediated through ERK1/2 pathway, in human adenoid cystic carcinoma cells (Freitas et al, 2004(Freitas et al, , 2007de Siqueira, Freitas and Jaeger, 2022).…”

“…However, due to many possibilities of the variant chain arrangements, which can give around 60 potential molecules of laminin, the chain subunits now designate the specific laminin. For instance, the isoform Laminin-111 (named before as Laminin 1) received this name due to the subunits being α1, β1 and γ1 (Aumailley et al, 2005;Hohenester, 2019;de Siqueira, Freitas and Jaeger, 2022). Besides that, the isoforms seem to be cell and tissue specific distributed.…”

“…Therefore, the effects from laminin-111 have been uncovered with the help of its synthetic sequences, which usually have around 6-12 amino acids. Moreover, these bioactive peptides can trigger effects as: cell protection against malignancy, migration (in wound healing and tumor), invasion, angiogenesis, secretion of proteases, invadopodia formation, alteration in signaling pathways, tumor growth, metastasis, and others (Ponce, Nomizu and Kleinman, 2001;Kuratomi et al, 2002;Engbring and Kleinman, 2003;Freitas et al, 2004;Nascimento et al, 2010;Siqueira et al, 2016;Smuczek, 2019;Caires-dos-Santos et al, 2020;de Siqueira, Freitas and Jaeger, 2022). From several bioactive peptides that show important roles, some have been further investigated, for instance: YIGSR, IKVAV, AG73, C16 (Figure 2.2).…”

“…As the objective of this study, peptide C16 (KAFDITYVRLKF), localized at the first globular domain at the γ1-chain of laminin-111 has been shown to induce adhesion, migration, proteolytic activity and invadopodia formation and activity (Kuratomi et al, 2002;Pinheiro et al, 2011;Kikkawa et al, 2013;Siqueira et al, 2016;Smuczek, 2019;de Siqueira, Freitas and Jaeger, 2022).…”

“…Figure 2.2: Laminin-111 and its main bioactive peptides. Schematic model of Laminin-111, depicting the sites of protease cleavage and release of the peptides YGSR at the β1 chain, C16 at the γ1 chain, IKVAV at the α1 chain, and AG73, at the globular domain (LG4) of the α1 chain.Adapted fromde Siqueira, Freitas and Jaeger, 2022. …”