China's Changing Outbound Foreign Direct Investment Profile: Drivers and Policy Implications

After decades of negligible outbound foreign direct investment (FDI), Chinese firms' outbound investment has reached significant levels in recent years, challenging international investment norms and affecting international relations. But China's outflows are poorly understood. Seen in context, China is a laggard in global investment, and the country faces numerous internal impediments to overcoming this disadvantaged position. Daniel H. Rosen and Thilo Hanemann review the data behind China's growing outbound investment, consider the commercial and political forces driving this growth, and analyze both foreign and domestic obstacles for Chinese overseas investors. While extensive media coverage has provoked worries that Chinese firms are buying up the world, China remains a relatively minor global investor compared with OECD countries. China's net FDI position remains negative, with $5 of FDI assets under foreign ownership in China for every$1 of Chinese direct investment assets abroad. But China's efforts to rebalance its economic growth and make the shift toward higher value-added economic activity will increasingly force Chinese firms to invest abroad. Government policy has evolved in recent years to encourage and support China's firms to look abroad. Investment regimes in host countries are one obstacle to Chinese outbound FDI, but China's firms are even more impeded by home-made problems, including the parochial executive leadership and a dearth of key management skills needed to operate successfully overseas. Rosen and Hanemann argue that the growing volume and changing nature of China's outbound investment have important implications for policymakers in host countries. Host country governments must clarify their policies and draw a clearer line between legitimate national security reviews and protectionist economic competitiveness impulses disguised as security concerns. The lack of data transparency contributes to the poor understanding of China's outbound investment, and these inadequacies must be corrected if China and investment incumbents are to work together optimally. In addition, given its disadvantaged FDI starting position China should be expected to pull considerable weight to preserve and promote an open international investment environment, including by maintaining openness at home. If China converges upward to OECD outbound investment levels rather than incumbent leaders trimming down to historic Chinese levels due to protectionism, then future flows coming from China can contribute positively to a range of international issues, from financial crisis recovery to mitigating climate change.

Chinese FDI in the United States is taking off: How to maximize its benefits?

China‘s outward foreign direct investment (OFDI) grew rapidly in the past decade, but flows to developed economies have been limited. Now China‘s direct investment flows to the United States are poised to rise substantially. This new trend offers tremendous opportunities for the U. S., provided policymakers take steps to keep the investment environment open and utilize China‘s new interest productively

中国对美国直接投资快速增长：如何获得最大化的收益？

过去十年，中国的对外直接投资快速增长，但对发达经济体的投资十分有限。目前，中国对美国的投资快速增长。如果政策制定者能够采取措施保持开放的投资环境，并有效利用中国新增投资，那么这种新趋势将为美国提供巨大的机遇

Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival.

TAM family receptor tyrosine kinases comprising Tyro3 (Sky), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth. Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2. The benign character of merlin-deficient tumours makes them less responsive to chemotherapy. We previously showed that, amongst other growth factor receptors, TAM family receptors (Tyro3, Axl and Mer) are significantly overexpressed in schwannoma tissues. As Axl is negatively regulated by merlin and positively regulated by E3 ubiquitin ligase CRL4DCAF1, previously shown to be a key regulator in schwannoma growth we hypothesized that Axl is a good target to study in merlin-deficient tumours. Moreover, Axl positively regulates the oncogene Yes-associated protein, which is known to be under merlin regulation in schwannoma and is involved in increased proliferation of merlin-deficient meningioma and mesothelioma. Here, we demonstrated strong overexpression and activation of Axl receptor as well as its ligand Gas6 in human schwannoma primary cells compared to normal Schwann cells. We show that Gas6 is mitogenic and increases schwannoma cell-matrix adhesion and survival acting via Axl in schwannoma cells. Stimulation of the Gas6/Axl signalling pathway recruits Src, focal adhesion kinase (FAK) and NFκB. We showed that NFκB mediates Gas6/Axl-mediated overexpression of survivin, cyclin D1 and FAK, leading to enhanced survival, cell-matrix adhesion and proliferation of schwannoma. We conclude that Axl/FAK/Src/NFκB pathway is relevant in merlin-deficient tumours and is a potential therapeutic target for schwannoma and other merlin-deficient tumours

Artesunate induces necrotic cell death in schwannoma cells.

Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity

The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors

Merlin has broad tumor-suppressor functions as its mutations have been identified in multiple benign tumors and malignant cancers. In all schwannomas, the majority of meningiomas and 1/3 of ependymomas Merlin loss is causative. In neurofibromatosis type 2, a dominantly inherited tumor disease because of the loss of Merlin, patients suffer from multiple nervous system tumors and die on average around age 40. Chemotherapy is not effective and tumor localization and multiplicity make surgery and radiosurgery challenging and morbidity is often considerable. Thus, a new therapeutic approach is needed for these tumors. Using a primary human in vitro model for Merlin-deficient tumors, we report that the Ras/Raf/mitogen-activated protein, extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) scaffold, kinase suppressor of Ras 1 (KSR1), has a vital role in promoting schwannomas development. We show that KSR1 overexpression is involved in many pathological phenotypes caused by Merlin loss, namely multipolar morphology, enhanced cell-matrix adhesion, focal adhesion and, most importantly, increased proliferation and survival. Our data demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesion is more dependent on KSR1 than MEK1/2. Immunoprecipitation analysis reveals that KSR1 is a novel binding partner of Merlin, which suppresses KSR1's function by inhibiting the binding between KSR1 and c-Raf. Our proteomic analysis also demonstrates that KSR1 interacts with several Merlin downstream effectors, including E3 ubiquitin ligase CRL4DCAF1. Further functional studies suggests that KSR1 and DCAF1 may co-operate to regulate schwannomas formation. Taken together, these findings suggest that KSR1 serves as a potential therapeutic target for Merlin-deficient tumors