Akt/PKB is a serine/threonine protein kinase that functions as a critical regulator of cell survival and proliferation. Akt/PKB family comprises three highly homologous members known as PKBα/Akt1, PKBβ/Akt2 and PKBγ/Akt3 in mammalian cells. Similar to many other protein kinases, Akt/PKB contains a conserved domain structure including a specific PH domain, a central kinase domain and a carboxyl-terminal regulatory domain that mediates the interaction between signaling molecules. Akt/PKB plays important roles in the signaling pathways in response to growth factors and other extracellular stimuli to regulate several cellular functions including nutrient metabolism, cell growth, apoptosis and survival. This review surveys recent developments in understanding the molecular mechanisms of Akt/PKB activation and its roles in cell survival in normal and cancer cells.

Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the alpha(v)beta(3) integrins to increase cellular survival. These data demonstrated that the survival-promoting function is crucial for periostin to promote tumor metastasis of colon cancer.

Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia-inducible factors (HIFs). HIF-1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF-1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF-1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF-1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers.

Periostin, also termed osteoblast-specific factor 2, is a matricellular protein with known functions in osteology, tissue repair, oncology, cardiovascular and respiratory systems, and in various inflammatory settings. However, most of the research to date has been conducted in divergent and circumscribed areas meaning that the overall understanding of this intriguing molecule remains fragmented. Here, we integrate the available evidence on periostin expression, its normal role in development, and whether it plays a similar function during pathologic repair, regeneration, and disease in order to bring together the different research fields in which periostin investigations are ongoing. In spite of the seemingly disparate roles of periostin in health and disease, tissue remodeling as a response to insult/injury is emerging as a common functional denominator of this matricellular molecule. Periostin is transiently upregulated during cell fate changes, either physiologic or pathologic. Combining observations from various conditions, a common pattern of events can be suggested, including periostin localization during development, insult and injury, epithelial–mesenchymal transition, extracellular matrix restructuring, and remodeling. We propose mesenchymal remodeling as an overarching role for the matricellular protein periostin, across physiology and disease. Periostin may be seen as an important structural mediator, balancing appropriate versus inappropriate tissue adaption in response to insult/injury.

Periostin, also called osteoblast-specific factor 2 (OSF-2), is a member of the fasciclin family and a disulfide-linked cell adhesion protein that has been shown to be expressed preferentially in the periosteum and periodontal ligaments, where it acts as a critical regulator of bone and tooth formation and maintenance. Furthermore, periostin plays an important role in cardiac development. Recent clinical evidence has also revealed that periostin is involved in the development of various tumors, such as breast, lung, colon, pancreatic, and ovarian cancers. Periostin interacts with multiple cell-surface receptors, most notably integrins, and signals mainly via the PI3-K/Akt and other pathways to promote cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, aspects related to the function of periostin in tumorigenesis are summarized.