Atsuko Yonemura
Research Subjects
Research Interests
Atsuko Yonemura has a total of 25 co-authors. Here are the top co-authors by number of shared publications:
- Akiho Nishimura
Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; Gastrointestinal Cancer Biology, International Research Center of Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan
1 shared publication - Feng Wei
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, and
1 shared publication - Fumimasa Kitamura
Surgical Gastroenterology, Amakusa Regional Medical Center, Amakusa, JPN
1 shared publication - Hideo Baba
Institute of Pathology, University Hospital Essen, University Duisburg-Essen, Germany (D.M., H.A.B.).
1 shared publication - Hiromitsu Hayashi
Department of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
1 shared publication - Huaitao Wang
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, and
1 shared publication
Latest Publications
- Top Cited PapersOpen Access
- 23 October 2023
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 8 (20)
Cancer-associated fibroblasts reuse cancer-derived lactate to maintain a fibrotic and immunosuppressive microenvironment in pancreatic cancer
Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.
- 23 October 2023
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 8 (20)
Top Cited PapersOpen AccessCancer-associated fibroblasts reuse cancer-derived lactate to maintain a fibrotic and immunosuppressive microenvironment in pancreatic cancer
Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.