5 results on '"Sasaki, Atsuo T"'
Number of results to display per page
Search Results
2. IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma
- Author
-
Kofuji, Satoshi, Kofuji, Satoshi, Hirayama, Akiyoshi, Eberhardt, Alexander Otto, Kawaguchi, Risa, Sugiura, Yuki, Sampetrean, Oltea, Ikeda, Yoshiki, Warren, Mikako, Sakamoto, Naoya, Kitahara, Shuji, Yoshino, Hirofumi, Yamashita, Daisuke, Sumita, Kazutaka, Wolfe, Kara, Lange, Lisa, Ikeda, Satsuki, Shimada, Hiroko, Minami, Noriaki, Malhotra, Akshiv, Morioka, Shin, Ban, Yuki, Asano, Maya, Flanary, Victoria L, Ramkissoon, Annmarie, Chow, Lionel ML, Kiyokawa, Juri, Mashimo, Tomoyuki, Lucey, Greg, Mareninov, Sergey, Ozawa, Tatsuya, Onishi, Nobuyuki, Okumura, Koichi, Terakawa, Jumpei, Daikoku, Takiko, Wise-Draper, Trisha, Majd, Nazanin, Kofuji, Kaori, Sasaki, Mika, Mori, Masaru, Kanemura, Yonehiro, Smith, Eric P, Anastasiou, Dimitrios, Wakimoto, Hiroaki, Holland, Eric C, Yong, William H, Horbinski, Craig, Nakano, Ichiro, DeBerardinis, Ralph J, Bachoo, Robert M, Mischel, Paul S, Yasui, Wataru, Suematsu, Makoto, Saya, Hideyuki, Soga, Tomoyoshi, Grummt, Ingrid, Bierhoff, Holger, Sasaki, Atsuo T, Kofuji, Satoshi, Kofuji, Satoshi, Hirayama, Akiyoshi, Eberhardt, Alexander Otto, Kawaguchi, Risa, Sugiura, Yuki, Sampetrean, Oltea, Ikeda, Yoshiki, Warren, Mikako, Sakamoto, Naoya, Kitahara, Shuji, Yoshino, Hirofumi, Yamashita, Daisuke, Sumita, Kazutaka, Wolfe, Kara, Lange, Lisa, Ikeda, Satsuki, Shimada, Hiroko, Minami, Noriaki, Malhotra, Akshiv, Morioka, Shin, Ban, Yuki, Asano, Maya, Flanary, Victoria L, Ramkissoon, Annmarie, Chow, Lionel ML, Kiyokawa, Juri, Mashimo, Tomoyuki, Lucey, Greg, Mareninov, Sergey, Ozawa, Tatsuya, Onishi, Nobuyuki, Okumura, Koichi, Terakawa, Jumpei, Daikoku, Takiko, Wise-Draper, Trisha, Majd, Nazanin, Kofuji, Kaori, Sasaki, Mika, Mori, Masaru, Kanemura, Yonehiro, Smith, Eric P, Anastasiou, Dimitrios, Wakimoto, Hiroaki, Holland, Eric C, Yong, William H, Horbinski, Craig, Nakano, Ichiro, DeBerardinis, Ralph J, Bachoo, Robert M, Mischel, Paul S, Yasui, Wataru, Suematsu, Makoto, Saya, Hideyuki, Soga, Tomoyoshi, Grummt, Ingrid, Bierhoff, Holger, and Sasaki, Atsuo T
- Abstract
In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma. This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in glioblastoma reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for the occurance of aberrant nucleolar function and increased anabolic processes in glioblastoma, which constitutes a primary event in gliomagenesis.
- Published
- 2019
3. Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State
- Author
-
Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Garcia-Cao, Isabel, Song, Min Sup, Hobbs, Robin M., Laurent, Gaelle, Giorgi, Carlotta, de Boer, Vincent C. J., Anastasiou, Dimitrios, Ito, Keisuke, Sasaki, Atsuo T., Rameh, Lucia, Carracedo, Arkaitz, Cantley, Lewis C., Pinton, Paolo, Haigis, Marcia C., Pandolfi, Pier Paolo, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Garcia-Cao, Isabel, Song, Min Sup, Hobbs, Robin M., Laurent, Gaelle, Giorgi, Carlotta, de Boer, Vincent C. J., Anastasiou, Dimitrios, Ito, Keisuke, Sasaki, Atsuo T., Rameh, Lucia, Carracedo, Arkaitz, Cantley, Lewis C., Pinton, Paolo, Haigis, Marcia C., and Pandolfi, Pier Paolo
- Abstract
Decremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial artificial chromosome (BAC)-mediated transgenesis. The “Super-PTEN” mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake and increased mitochondrial oxidative phosphorylation and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and -independent pathways and negatively impacting two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect., National Institutes of Health (U.S.) (NIH grant R01 CA-82328-09), National Institutes of Health (U.S.) (NIH grant P01-CA089021), National Institutes of Health (U.S.) (NIH grant R01-GM41890), Italian Association for Cancer Research (grant), Spain. Ministerio de Educación y Ciencia, Human Frontier Science Program (Strasbourg, France) (Fellowships)
- Published
- 2014
4. Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses
- Author
-
Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Bellinger, Gary, Anastasiou, Dimitrios, Poulogiannis, George, Asara, John M., Boxer, Matthew B., Jiang, Jian-kang, Shen, Min, Gary, Bellinger, Sasaki, Atsuo T., Locasale, Jason W., Auld, Douglas S., Thomas, Craig J., Cantley, Lewis C., Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew G., Bellinger, Gary, Anastasiou, Dimitrios, Poulogiannis, George, Asara, John M., Boxer, Matthew B., Jiang, Jian-kang, Shen, Min, Gary, Bellinger, Sasaki, Atsuo T., Locasale, Jason W., Auld, Douglas S., Thomas, Craig J., and Cantley, Lewis C.
- Abstract
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys[superscript 358]. This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys[superscript 358] to Ser[superscript 358] oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress., National Institutes of Health (U.S.) (R03MH085679), National Institutes of Health (U.S.) (1P30CA147882), Burroughs Wellcome Fund, Damon Runyon Cancer Research Foundation, Smith Family Foundation, Starr Cancer Consortium
- Published
- 2013
5. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
- Author
-
Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew, Mattaini, Katherine Ruth, Metallo, Christian M., Vokes, Natalie I., Stephanopoulos, Gregory, Vander Heiden, Matthew G., Locasale, Jason W., Grassian, Alexandra R., Melman, Tamar, Lyssiotis, Costas A., Bass, Adam J., Heffron, Gregory J., Muranen, Taru, Sharfi, Hadar, Sasaki, Atsuo T., Anastasiou, Dimitrios, Mullarky, Edouard, Sasaki, Mika, Beroukhim, Rameen, Ligon, Azra H., Meyerson, Matthew L., Richardson, Andrea L., Chin, Lynda, Wagner, Gerhard, Asara, John M., Brugge, Joan S., Cantley, Lewis C., Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Vander Heiden, Matthew, Mattaini, Katherine Ruth, Metallo, Christian M., Vokes, Natalie I., Stephanopoulos, Gregory, Vander Heiden, Matthew G., Locasale, Jason W., Grassian, Alexandra R., Melman, Tamar, Lyssiotis, Costas A., Bass, Adam J., Heffron, Gregory J., Muranen, Taru, Sharfi, Hadar, Sasaki, Atsuo T., Anastasiou, Dimitrios, Mullarky, Edouard, Sasaki, Mika, Beroukhim, Rameen, Ligon, Azra H., Meyerson, Matthew L., Richardson, Andrea L., Chin, Lynda, Wagner, Gerhard, Asara, John M., Brugge, Joan S., and Cantley, Lewis C.
- Abstract
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood [1, 2]. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer., National Institutes of Health (U.S.), National Cancer Institute (U.S.), Smith Family Foundation, Damon Runyon Cancer Research Foundation, Burroughs Wellcome Fund
- Published
- 2013
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.