The transcription factor Foxa2 is implicated in blood glucose homeostasis. Conditional expression of Foxa2 or its dominant-negative mutant DN-Foxa2 in INS-1 cells reveals that Foxa2 regulates the expression of genes important for glucose sensing in pancreatic β-cells. Overexpression of Foxa2 results in blunted glucose-stimulated insulin secretion, whereas induction of DN-Foxa2 causes a left shift of glucose-induced insulin release. The mRNA levels of GLUT2 and glucokinase are drastically decreased after induction of Foxa2. In contrast, loss of Foxa2 function leads to up-regulation of hexokinase (HK) I and II and glucokinase (HK-IV) mRNA expression. The glucokinase and the low K _mhexokinase activities as well as glycolysis are increased proportionally. In addition, induction of DN-Foxa2 also reduces the expression of β-cell K_ATP channel subunits Sur1 and Kir6.2 by 70%. Furthermore, in contrast to previous reports, induction of Foxa2 causes pronounced decreases in the HNF4α and HNF1α mRNA levels. Foxa2 fails to regulate the expression of Pdx1 transcripts. The expression of insulin and islet amyloid polypeptide is markedly suppressed after induction of Foxa2, while the glucagon mRNA levels are significantly increased. Conversely, Foxa2 is required for glucagon expression in these INS-1-derived cells. These results suggest that Foxa2 is a vital transcription factor evolved to control the expression of genes essential for maintaining β-cell glucose sensing and glucose homeostasis.

It has been confirmed that platelets play a key role in tumorigenesis. Tumor-activated platelets can recruit blood cells and immune cells to migrate, establish an inflammatory tumor microenvironment at the sites of primary and metastatic tumors. On the other hand, they can also promote the differentiation of mesenchymal cells, which can accelerate the proliferation, genesis and migration of blood vessels. The role of platelets in tumors has been well studied. However, a growing number of studies suggest that interactions between platelets and immune cells (e.g., dendritic cells, natural killer cells, monocytes, and red blood cells) also play an important role in tumorigenesis and tumor development. In this review, we summarize the major cells that are closely associated with platelets and discuss the essential role of the interaction between platelets with these cells in tumorigenesis and tumor development.

Inflammation involves interactions between various immune cells, inflammatory cells, chemokines and cytokines in pancreatic cancer. Cancer cells as well as surrounding stromal and inflammatory cells establish an inflammatory tumor microenvironment (TME). Inflammation is closely associated with immunity. Meanwhile, immune cells are involved in both inflammation and immune response. Tumor-promoting inflammation and tumor-suppressive immunity are two main characteristics of the tumor microenvironment in pancreatic cancer. Yet, the mechanism of inflammation and immune response in pancreatic cancer development is still unclear due to the dual role of some cytokines and the complicated crosstalk between tumor and stromal components in TME. In this review, we outline the principal cytokines and stromal cells in the pancreatic TME that are involved in the tumor-promoting and immunosuppressive effects of inflammation, and discuss the interaction between inflammation and stromal components in pancreatic cancer progression. Moreover, the clinical approaches based on targeting TME in pancreatic cancer are also summarized. Defining the mechanisms of interplay between inflammation and stromal components will be essential for further development of anti-cancer therapies.

Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.