7th Floor, Seminar Room 1, IDAC Center for Basic Aging Research
Title
Intracellular connexin protein – its ability to enhance self-renewal of cancer stem cells via induction of adaptive response to ER-stress
Speaker
OMORI Yasufumi
Affiliation
Department of Molecular and Tumour Pathology, Akita University Graduate School
Organizer
OKADA Yoshinori (Department of Thoracic Surgery・ext 8520)
Abstract
Connexin (Cx) is a unique component of gap junction (GJ), which is, however, not a unique function of Cx. Today, Cx is beyond GJ, i.e., Cx can function as GJ-independent hemichannels and even as mitochondrial Cx. It is incontestable that GJ is tumor-suppressive and impaired in an early stage of carcinogenesis. Although aberrant localization of Cx in intracellular domains is one of mechanisms causing disruption of GJ in tumor cells, the amount of intracellular Cx continues to increase during progression in various human cancers, thus suggesting that intracellular Cx should be not only a loss-of-function form but also favorable for cancer progression such as invasion and metastasis. Our group has found that an excessive amount of intracellular Cx induces metastasis both in vitro and in vivo and that intracellular Cx has the potential to enhance self-renewal of cancer stem cells by exploiting a pathway driving an adaptive but not destructive response to endoplasmic reticulum stress. Taken together, while Cx-mediated GJ suppresses carcinogenesis, intracellular accumulation of Cx promotes cancer progression once a tumor has developed.
