Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness

Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes

カイゴ フクシカ ニ オケル ソツギョウ ジ キョウツウ シケン ノ トリクミ ガッカ FD カツドウ ノ イッカン トシテ ノ ソツギョウジ キョウツウ シケン

All students in the nursing care department must take the general graduate examination. The result does not afect students\u27 acquisition of the national license now. However, it is expected that each student must pass the examination to get the license in the future. We, professors in the nursing care department, educate and encourage them through various opportunities to become good care workers. The goal of passing the examination becomes more diicult year after year as a whole, for the acknowledged level of students lowers year after year. However, the knowledge of nursing care is critically important in providing appropriate nursing care. Therefore all the professors of the department determined to educate all the students in order to pass the examination. It is a hard object for the professors to attain. We must improve our teaching skills through our faculty development activities. Last year we had many special lessons for our students to prepare the examination. The number of passing the examination improved amazingly last year, compared to the previous year. We will continue to improve our teaching skills to attain our goal, to make sure all the students pass the examinat ion

Environmental History of Waterfront Life －Folk Cultures in Brackish Water Environments－

This joint research focuses on brackish water environments. Many of the coastal environments of the Japanese archipelago, such as estuaries, lagoons ― parts of back swamps ― and semi-enclosed bays, are in brackish water areas, where freshwater and sea water mix. Being low-lying, marshy and mixed with salt water, these areas are barren land where people usually do not live, and have been regarded as poor soil that must be transformed by, for example, developing new rice fields.　However, this is how brackish water areas have been looked at mainly by those in governments. It goes without saying that historians depending on records and statistics kept for governments have looked at these areas in the same way. How will brackish water environments look if examined from the viewpoints of people who have lived there instead of the viewpoints of researchers and those in governments ? This question gave our joint research a purpose : presenting a new image of brackish water environments.　This paper has been compiled as an interim report, and consists of articles by the following five joint researchers :　Yasumuro Satoru has drawn up an outline of the history of research on brackish water conducted to date, and presented a definition of brackish water at this point for us to carry out our joint research. He has also reported on fisheries characteristic of downstream brackish water areas and brackish lakes, and examined contemporary issues concerning brackish water, relating these issues to environmental issues.　Matsuda Mutsuhiko has reviewed folklore research conducted to date on the impacts of brackish lakes on fisheries, taking into account the achievements of ecology. He has also conducted a preliminary study to clarify a relationship between various fishery methods employed in brackish lakes and the lives of people involved in fisheries there.　Yamamoto Shino looks at commercial activities linked to brackish lakes. On Daikon Island in Nakaumi, a brackish lake on the border between Shimane and Tottori prefectures, many women peddled peony seedlings from the 1960s to the 70s. She has used various reports compiled in the 1950s as texts to review the livelihood on Daikon Island from the prewar to postwar years and examine why the peddling started.　Kawashima Shuichi studies ria coast bays, which are brackish water environments. As ria coasts, where rivers flow directly into the sea from mountains, create nutrient-rich brackish water environments, many kinds of fish are attracted to ria coast bays. He has reported on the history of fisheries from the early modern period, including competing interests such as salt farming in bay areas that tried to eliminate brackish water environments and mullet net fishing that took advantage of brackish water environments, in villages facing Kesennuma Bay in Miyagi Prefecture, a typical ria coast brackish bay.　Lastly, Tsunemitsu Toru looks at fisheries techniques used in brackish water areas at estuaries. Although sweetfish bait fishing is a fisheries technique noticeable in brackish water areas, little attention has been paid to it in the field of folklore. He has reported on bait fishing in the Kure River in Nakatosa Town, Kochi Prefecture, from the mid-1950s to the mid-1960s based on his own experiences.① 水上生活者の歴史的変容（水上生活班） ② 汽水域の民俗文化（汽水班