Laminins and cancer progression

Abstract

Laminins (αβγ heterotrimers) form the basement membrane. They are important for many cell processes, through adhesion and signaling. There are 17 known laminins with different properties, depending on their subunits. Among the many functions fulfilled by laminins, they actively contribute to all stages of cancer progression, from the onset of the disease to the life-threatening development of metastases. At the cellular level, laminins are crucial in helping cells adhere, migrate, and differentiate. Following the six hallmarks of cancer (self-sufficiency in growth signals, sustained angiogenesis, evading apoptosis, insensitivity to antigrowth signals, limitless replicative potential, and the ability for tissue invasion and metastasis), this chapter will outline available data involving laminins and their receptors in cell proliferation, death, angiogenesis, and cancer invasion and metastasis. In light of those evidences, there is no doubt that laminins are able to regulate all stages of cancer progression, either directly or in partnership with receptors and coreceptors. Two laminins (laminin-111 and -332) are particularly active in carcinogenesis, while others seem to be more specific to angiogenesis (laminin-211, -213, and -221) or motility (laminin-511). Furthermore, laminins can activate different receptors, which induce different signaling pathways. Some are redundant to laminin functions (PI-3K, FAK, ERK), and others are only activated in a particular context, such as the laminin-induced relocation to the nucleus of transcription factors. Overall, this chapter updates our knowledge on the role played by laminins in cancer. By integrating the latest developments in the field, this review helps elucidate how these proteins can be at the center of new diagnostic tools, prognostic power, and therapeutic strategies in the fight against cancer. © Springer Science+Business Media, LLC 2010. All rights reserved.