Article
Multidisciplinary Sciences
Kelsie J. Anson, Giulia A. Corbet, Amy E. Palmer
Summary: In this study, the researchers investigated how changes in intracellular zinc ion levels affect kinase signaling pathways using fluorescent biosensors and cell perturbations. The results showed that zinc ion fluctuations are not toxic and do not activate stress-dependent kinase signaling. Additionally, the study demonstrated that while zinc ions can inhibit phosphatases, ERK and Akt are primarily activated through upstream signaling pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Carline Chaves-Almagro, Johanna Auriau, Alizee Dortignac, Pascal Clerc, Hubert Lulka, Simon Deleruyelle, Fabrice Projetti, Jessica Nakhle, Audrey Frances, Judit Berta, Veronique Gigoux, Daniel Fourmy, Marlene Dufresne, Anne Gomez-Brouchet, Julie Guillermet-Guibert, Pierre Cordelier, Bernard Knibiehler, Ralf Jockers, Philippe Valet, Yves Audigier, Bernard Masri
Summary: This study investigated the expression and protumoral function of apelin and its receptor APJ in human pancreatic adenocarcinoma. It was found that apelin and APJ were co-expressed by tumor cells in the invasive stage, and apelin promoted cancer cell proliferation, migration, and glucose uptake. Blocking the apelin receptor reduced cancer cell proliferation and pancreatic tumor burden.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Antonia Schubert, Michael Boutros
Summary: Extracellular vesicles (EVs) have emerged as potential diagnostic and prognostic markers for cancer therapy, yet much remains unknown about their exact mechanisms of signaling specificity and cargo transfer. Several signaling cascades utilize EVs for signaling in tumor-stroma interaction, including key pathways such as Wnt and TGF-beta, which are tightly associated with tumor progression and metastasis. Multiple mechanisms of how EVs interplay with signaling cascades to mediate complex processes have been described, shedding light on the potential therapeutic applications and gaps in knowledge.
MOLECULAR ONCOLOGY
(2021)
Article
Gastroenterology & Hepatology
Lu Tian, Luqing Zhao, Karen Man-Fong Sze, Charles Shing Kam, Vanessa Sheung-In Ming, Xia Wang, Vanilla Xin Zhang, Daniel Wai-Hung Ho, Tan-To Cheung, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: RalA is significantly up-regulated in HCC patients and associated with aggressive tumor behavior and poor prognosis. Its up-regulation is driven by copy number gain, while RalGAPA2 knockdown increases RalA activity. Tumors with down-regulated RalGAPA2 and up-regulated RalA display more aggressive behavior and poorer survival, with Ral inhibition showing potential as a therapeutic approach.
Article
Oncology
Antonella Catalano, Mojca Adlesic, Thorsten Kaltenbacher, Rhena F. U. Klar, Joachim Albers, Philipp Seidel, Laura P. Brandt, Tomas Hejhal, Philipp Busenhart, Niklas Roehner, Kyra Zodel, Kornelia Fritsch, Peter J. Wild, Justus Duyster, Ralph Fritsch, Tilman Brummer, Ian J. Frew
Summary: The study demonstrates that the combined use of MEK and ERK inhibitors can prevent the emergence of drug resistance, but may not be effective if cancer cells are resistant to single agents. Drug resistance involves complex rewiring of cellular kinase signaling networks, which are not overlapping between different cancer cell lines. The identification of new drug sensitivities in some resistant cells suggests potential additional therapeutic targets in oncogenic RAS-driven tumors.
Article
Biotechnology & Applied Microbiology
Yuxiao Zheng, Feng Qi, Lu Li, Bin Yu, Yifei Cheng, Minghui Ge, Chao Qin, Xiao Li
Summary: This study identified lncNAP1L6 as an oncogene in prostate cancer (PCa) and suggested it as a potential therapeutic target. Functional assays revealed that lncNAP1L6 promotes cell migration, invasion, and epithelial-mesenchymal transition (EMT) in PCa. Mechanism assays showed that lncNAP1L6 regulates NAP1L2 mRNA stability through METTL14/METTL3 complex-mediated m6A methylation and interacts with YY1 to activate MMP signaling pathway.
CANCER GENE THERAPY
(2023)
Article
Oncology
Yuxiao Chang, Ziran Huang, Fengyi Hou, Yuejiao Liu, Likun Wang, Zhen Wang, Yifan Sun, Zhiyuan Pan, Yafang Tan, Lei Ding, Hong Gao, Ruifu Yang, Yujing Bi
Summary: This study revealed an important relationship between Parvimonas micra (P. micra) and colorectal cancer (CRC) through cell experiments and mouse models. Transcriptomics and microRNA sequencing showed that P. micra promoted CRC development through the activation of the miR-218-5p/Ras/ERK/c-Fos pathway.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Xiaochen Li, Xiaopei Cao, Hanqiu Zhao, Mingzhou Guo, Xiaoyu Fang, Ke Li, Lu Qin, Yuanzhou He, Xiansheng Liu
Summary: Hypoxia activates the Notch4-ERK/JNK/P38 MAPK signaling pathway to promote the proliferation, migration, and anti-apoptotic effects of LUAD cells. Notch4 plays a key role in the growth and metastasis of LUAD. Inhibitors of ERK, JNK, and P38 can partially reverse the effects of Notch4.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Juan Liu, Cen Zhang, Tianliang Zhang, Chun-Yuan Chang, Jianming Wang, Ludvinna Bazile, Lanjing Zhang, Bruce G. G. Haffty, Wenwei Hu, Zhaohui Feng
Summary: The glycolytic enzyme lactate dehydrogenase A (LDHA) activates small GTPase Rac1 to promote cancer independently of its glycolytic enzyme activity. LDHA interacts with the active form of Rac1, Rac1-GTP, to inhibit Rac1-GTP interaction with its negative regulator, GTPase-activating proteins, leading to Rac1 activation. LDHA overexpression in clinical breast cancer specimens is associated with higher Rac1 activity. Inhibition of Rac1 suppresses the oncogenic effect of LDHA. Combination inhibition of LDHA enzyme activity and Rac1 activity displays a synergistic inhibitory effect on breast cancers with LDHA overexpression.
Article
Oncology
Xiuhe Zou, Qian Zhou, Yan Nie, Junhe Gou, Jing Yang, Jingqiang Zhu, Zhihui Li, Yanping Gong
Summary: This study found that TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.
Article
Cell Biology
Eunice Cho, Hua Jane Lou, Leena Kuruvilla, David A. Calderwood, Benjamin E. Turk
Summary: This study identifies PPP6C as a crucial phosphatase for MEK in the ERK pathway, which is frequently mutated or downregulated in melanoma. Loss of PPP6C leads to hyperphosphorylation of MEK, enhancing signaling through the pathway and reducing sensitivity to MEK inhibitors. Its recurrent mutations in melanoma cause MEK hyperphosphorylation, suggesting their role in promoting the disease by activating the core oncogenic pathway.
Article
Medicine, Research & Experimental
Shion A. Lim, Jie Zhou, Alexander J. Martinko, Yung-Hua Wang, Ekaterina V. Filippova, Veronica Steri, Donghui Wang, Soumya G. Remesh, Jia Liu, Byron Hann, Anthony A. Kossiakoff, Michael J. Evans, Kevin K. Leung, James A. Wells
Summary: Selective antibodies that recognize proteolytic neoepitopes on CDCP1 have the potential to improve the effectiveness and safety of treatments for solid tumors. These antibodies, generated through differential phage display, specifically target cleaved CDCP1-expressing cancer cells and exhibit tumor-specific localization and antitumor activity. Compared to pan-CDCP1 approaches, they offer superior safety profiles.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Biochemistry & Molecular Biology
Shiela C. C. Samson, Akib M. M. Khan, Michelle C. C. Mendoza
Summary: The RAS-ERK pathway is crucial in promoting cell migration and invasion, with steady-state ERK activity playing a role in promoting both single cell and collective migration and invasion. ERK drives actin polymerization and adhesion turnover for edge protrusion, while cell contraction stimulates cell movement in epithelial sheets.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Koki Kohashi, Yusuke Mori, Rika Narumi, Kei Kozawa, Tomoko Kamasaki, Susumu Ishikawa, Mihoko Kajita, Rei Kobayashi, Yoichiro Tamori, Yasuyuki Fujita
Summary: The study reveals the potential role of cell competition in the development of cancer, as multiple oncogenic mutations accumulate within epithelial tissues. Through investigating the consecutive mutations of Ras and Scribble, it is discovered that mitochondrial metabolism plays a key role in the competitive interaction between double-and single-mutant cells. Further research on this competitive interaction could lead to new approaches for cancer treatment based on cell competition, preventing the clonal expansion of more malignant populations within tumors.
Review
Oncology
Kelvin K. Tsai, Byoung-Il Bae, Chung-Chi Hsu, Li-Hsin Cheng, Yuval Shaked
Summary: Despite recent advances in targeted therapies and immunotherapies, effective treatment for advanced-stage cancers is still a clinical need. Identifying the driver mechanisms of cancer aggressiveness is crucial for developing breakthrough therapeutic strategies. ASPM has been found to play a critical role in regulating cancer stemness and aggressiveness in various malignant tumor types. This review summarizes the domain compositions, expression patterns, and prognostic significance of ASPM in cancers, as well as its role as a regulatory hub in development- and stemness-associated signaling pathways and DNA repair in cancer cells. The review highlights the potential utility of ASPM as a prognostic biomarker and therapeutic target.
Article
Clinical Neurology
Koichi Ichimura, Shintaro Fukushima, Yasushi Totoki, Yuko Matsushita, Ayaka Otsuka, Arata Tomiyama, Tohru Niwa, Hirokazu Takami, Taishi Nakamura, Tomonari Suzuki, Kohei Fukuoka, Takaaki Yanagisawa, Kazuhiko Mishima, Yoichi Nakazato, Fumie Hosoda, Yoshitaka Narita, Soichiro Shibui, Akihiko Yoshida, Akitake Mukasa, Nobuhito Saito, Toshihiro Kumabe, Masayuki Kanamori, Teiji Tominaga, Keiichi Kobayashi, Saki Shimizu, Motoo Nagane, Toshihiko Iuchi, Masahiro Mizoguchi, Koji Yoshimoto, Kaoru Tamura, Taketoshi Maehara, Kazuhiko Sugiyama, Mitsutoshi Nakada, Keiichi Sakai, Yonehiro Kanemura, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Nobutaka Kawahara, Tatsuya Takayama, Masahiro Yao, Mamoru Kato, Hiromi Nakamura, Natsuko Hama, Ryuichi Sakai, Toshikazu Ushijima, Masao Matsutani, Tatsuhiro Shibata, Ryo Nishikawa
ACTA NEUROPATHOLOGICA
(2016)
Article
Oncology
Atsushi Goto, Hiroshi Noto, Mitsuhiko Noda, Kohjiro Ueki, Masato Kasuga, Naoko Tajima, Ken Ohashi, Ryuichi Sakai, Shoichiro Tsugane, Nobuyuki Hamajima, Kazuo Tajima, Kohzoh Imai, Hitoshi Nakagama
Article
Cell Biology
Hideki Yamaguchi, Yuumi Ito, Nami Miura, Yuko Nagarnura, Ayaka Nakabo, Kiyoko Fukami, Kazufumi Honda, Ryuichi Sakai
EUROPEAN JOURNAL OF CELL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Yutaro Yamamoto, Arata Tomiyama, Nobuyoshi Sasaki, Hideki Yamaguchi, Takuya Shirakihara, Katsuhiko Nakashima, Kosuke Kumagai, Satoru Takeuchi, Terushige Toyooka, Naoki Otani, Kojiro Wada, Yoshitaka Narita, Koichi Ichimura, Ryuichi Sakai, Hiroki Namba, Kentaro Mori
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Shingo Miyamoto, Yuko Nagamura, Ayaka Nakabo, Akira Okabe, Kazuyoshi Yanagihara, Kiyoko Fukami, Ryuichi Sakai, Hideki Yamaguchi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Oncology
Tadashi Sawayama, Katsuhiko Nakashima, Tohru Ichimura, Ryuichi Sakai, Takamasa Uekita
Article
Oncology
Ken Yamashita, Shinichi Kiyonari, Shoma Tsubota, Satoshi Kishida, Ryuichi Sakai, Kenji Kadomatsu
Article
Multidisciplinary Sciences
Sho Kakizawa, Yasushi Kishimoto, Shinichiro Yamamoto, Kazuko Onga, Kunihiko Yasuda, Yoshiaki Miyamoto, Masahiko Watanabe, Ryuichi Sakai, Nozomu Mori
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Yuko Nagamura, Makoto Miyazaki, Yoshiko Nagano, Masako Yuki, Kiyoko Fukami, Kazuyoshi Yanagihara, Kazuki Sasaki, Ryuichi Sakai, Hideki Yamaguchi
Summary: This study identified PLEKHA5 as a protein downstream of Met that is tyrosine-phosphorylated in DGC cells with Met gene amplification. Knockdown of PLEKHA5 selectively suppressed the growth of these cells by inducing apoptosis and abrogated malignant phenotypes, suggesting its essential role in Met-addicted DGC progression. Mechanistically, PLEKHA5 dysregulation of glycolytic metabolism activates the JNK pathway to promote apoptosis.
Article
Oncology
Yuko Nagamura, Makoto Miyazaki, Yoshiko Nagano, Arata Tomiyama, Rieko Ohki, Kazuyoshi Yanagihara, Ryuichi Sakai, Hideki Yamaguchi
Summary: Diffuse-type gastric carcinoma (DGC) is characterized by aggressive progression associated with rapid infiltrative growth, massive fibrosis, and peritoneal dissemination. In this study, SHP2 was identified as a critical regulator downstream of the amplified Met and FGFR2 receptor tyrosine kinases (RTKs) in DGC cell lines. Targeting SHP2 selectively suppressed the growth and malignant phenotypes of RTK-addicted DGC, highlighting its potential as a therapeutic target for DGC treatment.
Article
Oncology
Shingo Miyamoto, Yoshiko Nagano, Makoto Miyazaki, Yuko Nagamura, Kazuki Sasaki, Takeshi Kawamura, Kazuyoshi Yanagihara, Toshio Imai, Rieko Ohki, Masakazu Yashiro, Masato Tanaka, Ryuichi Sakai, Hideki Yamaguchi
Summary: The study revealed that integrin alpha 5 plays a crucial role in mediating the heterotypic cancer cell-fibroblast interaction during peritoneal dissemination of DGC, suggesting it may be a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Takuya Shirakihara, Hideki Yamaguchi, Tadashi Kondo, Masakazu Yashiro, Ryuichi Sakai
Summary: The study reveals that in diffuse-type gastric cancer cells, transferrin receptor 1 (TfR1) binds and phosphorylates with fibroblast growth factor receptor 2 (FGFR2), promoting cell proliferation and tumorigenicity. This suggests that controlling TfR1 function could serve as a therapeutic target in diffuse-type gastric cancer with activated FGFR2.
Article
Cell Biology
Makoto Miyazaki, Ryo Otomo, Yuko Matsushima-Hibiya, Hidenobu Suzuki, Ayana Nakajima, Naomi Abe, Arata Tomiyama, Koichi Ichimura, Koichi Matsuda, Toshiki Watanabe, Takahiro Ochiya, Hitoshi Nakagama, Ryuichi Sakail, Masato Enari
CELL DEATH DISCOVERY
(2018)
Article
Oncology
Katsuhiko Nakashima, Takamasa Uekita, Shigenobu Yano, Jun-ichi Kikuchi, Ruri Nakanishi, Nozomi Sakamoto, Keisuke Fukumoto, Akihiro Nomoto, Keisuke Kawamoto, Takashi Shibahara, Hideki Yamaguchi, Ryuichi Sakai
Article
Endocrinology & Metabolism
Atsushi Goto, Hiroshi Noto, Mitsuhiko Noda, Kohjiro Ueki, Masato Kasuga, Naoko Tajima, Ken Ohashi, Ryuichi Sakai, Shoichiro Tsugane, Nobuyuki Hamajima, Kazuo Tajima, Kohzoh Imai, Hitoshi Nakagama
DIABETOLOGY INTERNATIONAL
(2016)