Identification and characterization of CIP2A as a novel oncogenic inhibitor of PP2A

Inhibition of the tumor suppressor protein phosphatase 2A (PP2A) activity has been identified as one of the five key alterations required for human cell transformation. Regardless of this crucial role in human cancer development, the detailed mechanisms by which PP2A inhibition occurs in human cancers remain largely uncharacterized. PP2A regulates a plethora of cellular signaling cascades. One of the targets of PP2A is Myc oncoprotein, which is destabilized and degraded in response to PP2A-mediated dephosphorylation of Myc serine 62. In this study we identify Cancerous Inhibitor of PP2A (CIP2A) as a previously uncharacterized endogenous inhibitor of PP2A in human cancer cells. CIP2A inhibits PP2A activity leading to subsequent stabilization of the Myc protein. CIP2A promotes malignant growth of cancer cells in vitro and xenograft tumor formation in vivo and is overexpressed in cancer. Moreover, we explored the effect of CIP2A on global transcriptional profiles and validated a CIP2A-dependent transcriptional signature. Analysis of the CIP2A signature revealed both Myc-dependent and -independent functions for CIP2A. Importantly, we demonstrate that the CIP2A signature has clinical relevance in human breast cancer subtypes. Finally, we identify the genes potentially mediating the long-term growth suppression in CIP2A depleted cancer cells. Taken together, this work identifies CIP2A as a novel human oncoprotein and describes its function in cancer cells. These results may open novel possibilities for patient stratification and therapeutic intervention of cancer.

Kuokkavieraita historiantutkimuksen pidoissa?

Kirjallisuusarvostelu

Vastuullisella liiketoiminnalla kohti kestävää kehitystä

Kirjallisuusarvostelu

Kasvuympäristön tekijöiden yhteys kielen ja lukutaidon kehitykseen

Teemanumero: Lukivaikeus.

Miten nopea nimeäminen ennakoi lukutaitoa

Teemanumero: Lukivaikeus.

Kulttuurisista olemassaolon tavoista Indonesiassa

Kirja-arvio

Intra-organizational knowledge transfer in a Finnish multinational company

The ability of a multinational company to effectively transfer knowledge from one unit to another can create a great source of competitive advantage and is crucial for long-term success. However, in their attempts to disseminate existent knowledge across national boundaries, organizations encounter several obstacles. Especially challenging is the transfer of tacit knowledge, the most valuable kind, as it is embedded in the minds and the behavior of people. The purpose of this study is to identify the main factors and challenges to be considered in intra-organizational knowledge transfer and consequently develop a framework that could be utilized to improve the process. The research is of qualitative nature and it adopts an exploratory approach. The study was further conducted as an intensive single-case study through studying a Finnish multinational company, and the researcher adopted a role as a participant observant in the research setting. Other data collection methods include semi-structured interviews and an online survey. The research findings show that knowledge transfer is currently challenging within the international sales organization of the case company. The majority of knowledge is currently concentrated in the company headquarters, and it is not always systematically distributed to the regional offices abroad. The main factor affecting knowledge transfer seems to be the organizational culture, which does not support or encourage knowledge sharing. The company is struggling in having a common place for information and employees that lack proper social networks have difficulties accessing relevant knowledge. Some recommended improvement suggestions include the institutionalization of knowledge transfer by turning it into an articulated organizational goal, and the implementation of a reward system that includes soft factors, such as teamwork and knowledge sharing behavior. Furthermore, the organizational culture should be more open and supportive in order to reinforce trust. Individuals in regional offices should be given better support by offering them dedicated mentors and increasing the amount of expatriation. Finally, knowledge should actively be codified and stored in commonly shared platforms where it is easily accessible by all employees.

Opetus- ja kulttuuriministeriön puheenvuoro

Esitys Kirjastoverkkopäivillä 23.10.2012 Helsingissä