Article
Oncology
Jesus Gonzalez-Bosquet, Jamie N. Bakkum-Gamez, Amy L. Weaver, Michaela E. McGree, Sean C. Dowdy, Abimbola O. Famuyide, Benjamin R. Kipp, Kevin C. Halling, Fergus J. Couch, Karl C. Podratz
Summary: The study investigates the role of PI3K-AKT pathway in endometrial cancer and found that deficiencies in PP2A and E3UL are seminal biological drivers in EC, independent of PIK3CA mutations, PTEN mutations, and PIK3R1 mutations, as well as PIK3CA copy number variation. These deficiencies are associated with compromised progression-free survival and were prognostically discriminatory for certain tumor characteristics.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Scott P. Lyons, Elora C. Greiner, Lauren E. Cressey, Mark E. Adamo, Arminja N. Kettenbach
Summary: The PPP family is responsible for cellular serine and threonine dephosphorylation, achieving substrate specificity and selectivity by forming multimeric holoenzymes. Methylation plays a crucial role in regulating PPP holoenzyme assembly for PP2A, PP4, and PP6, with implications in human diseases like cancer and neurodegeneration. Endogenous PPP methylation is shown to have a crucial regulatory function in transformed and non-transformed cell lines in an isoform-specific manner.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jesus Gonzalez-Bosquet, S. John Weroha, Jamie N. Bakkum-Gamez, Amy L. Weaver, Michaela E. McGree, Sean C. Dowdy, Abimbola O. Famuyide, Benjamin R. Kipp, Kevin C. Halling, Siddhartha Yadav, Fergus J. Couch, Karl C. Podratz
Summary: The study aimed to evaluate the impact of molecular high-risk and low-risk stratification on the therapeutic efficacy of endometrial cancer. The study found that low-risk molecular parameters were associated with favorable treatment outcomes in clinically high-risk cancer, while high-risk molecular parameters were associated with risk of recurrence and insensitivity to adjuvant therapies.
Article
Multidisciplinary Sciences
Jesus Gonzalez-Bosquet, S. John Weroha, Jamie N. N. Bakkum-Gamez, Amy L. L. Weaver, Michaela E. E. McGree, Sean C. C. Dowdy, Abimbola O. O. Famuyide, Benjamin R. R. Kipp, Kevin C. C. Halling, Siddhartha Yadav, Fergus J. J. Couch, Karl C. C. Podratz
Summary: This study aimed to assess the ability of molecular stratification based on high-risk and low-risk subtypes to predict recurrence and sensitivity to chemotherapy or radiotherapy in endometrial cancer. The results showed significant differences in progression-free survival between high-risk and low-risk subtypes, and their association with clinicopathological risk factors. Molecular stratification status based on these subtypes could also predict response to adjuvant therapy and risk of recurrence.
Review
Medicine, General & Internal
Emma J. Crosbie, Sarah J. Kitson, Jessica N. McAlpine, Asima Mukhopadhyay, Melanie E. Powell, Naveena Singh
Summary: Endometrial cancer is the most common gynaecological cancer in high income countries, with a global rise in incidence. Obesity is the major underlying cause, posing challenges for diagnosis and treatment. Early presentation with postmenopausal bleeding ensures cure, but advanced cases have poor prognosis. Minimally invasive surgical staging and targeted chemotherapeutic strategies are important advances.
Article
Pharmacology & Pharmacy
Ze Peng, Tenzin Wangmu, Lingli Li, Guangsu Han, Dongmei Huang, Ping Yi
Summary: The combination of berberine and low glucose can inhibit the growth of gastric cancer through the activation of the PP2A/GSK38/MCL-1 signaling pathway, making it a new safe and effective anti-cancer therapy.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Philippe A. Cassier, Raul Navaridas, Melanie Bellina, Nicolas Rama, Benjamin Ducarouge, Hector Hernandez-Vargas, Jean-Pierre Delord, Justine Lengrand, Andrea Paradisi, Laurent Fattet, Gwenaele Garin, Hanane Gheit, Cecile Dalban, Ievgenia Pastushenko, David Neves, Remy Jelin, Nicolas Gadot, Nicolas Braissand, Sophie Leon, Cyril Degletagne, Xavier Matias-Guiu, Mojgan Devouassoux-Shisheboran, Eliane Mery-Lamarche, Justine Allard, Egor Zindy, Christine Decaestecker, Isabelle Salmon, David Perol, Xavi Dolcet, Isabelle Ray-Coquard, Cedric Blanpain, Agnes Bernet, Patrick Mehlen
Summary: Netrin-1 is found to be upregulated in most endometrial carcinomas (ECs). Blocking netrin-1 with an anti-netrin-1 antibody (NP137) effectively reduces tumor progression in an EC mouse model and shows promising results in a Phase I trial with advanced EC patients. NP137 induces cell death and inhibits epithelial-to-mesenchymal transition (EMT), resulting in reduced tumor EMT, changes in immune infiltrate, and enhanced interactions between cancer cells and the tumor microenvironment.
Review
Biochemistry & Molecular Biology
Irene Peris, Silvia Romero-Murillo, Carmen Vicente, Goutham Narla, Maria D. Odero
Summary: Protein phosphatase 2A (PP2A) inactivation is common in cancer due to the presence of regulatory B-subunits which determine substrate specificity and subcellular localization. Developing targeted therapies for specific PP2A complexes is a challenge in cancer treatment. The development of small molecules targeting PP2A-B56α has shown promise in treating solid and hematological tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Endocrinology & Metabolism
Madelaine J. Cho-Clark, Allison Watkins, T. John Wu
Summary: Since its discovery in the mammalian hypothalamus, gonadotropin-releasing hormone (GnRH) has been found in non-hypothalamic tissues and can have various functions in both the brain and periphery. Previous studies have targeted GnRH receptors (GnRHR) to treat reproductive cancers, but its metabolite GnRH-(1-5) acts differently through GPR101. This review focuses on the potential roles of GnRH-(1-5) in the periphery and its effects on endometrial cancer progression.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Jun Hao, Xinpei Ci, Yong Wang, Stephen Yiu Chuen Choi, Sarah E. Sullivan, Hui Xue, Rebecca Wu, Xin Dong, Anne M. Haegert, Colin C. Collins, Dong Lin, Yuzhuo Wang
Summary: The study revealed a reciprocal feedback between GRB10 and AR signaling, indicating the importance of GRB10 in the progression of prostate cancer.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Yusuke Hanaki, Yuki Shikata, Masayuki Kikumori, Mutsumi Okamura, Shingo Dan, Masaya Imoto, Kazuhiro Irie
Summary: A compound called 10-methyl-aplog-1 has been found to inhibit the proliferation of specific cancer cell lines without side effects. It achieves this by inhibiting PKCa and inducing PP2A-mediated attenuation of the Akt/S6 signaling axis, leading to G1 arrest in cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Milosz Pietrus, Kazimierz Pitynski, Marcin Waligora, Katarzyna Milian-Ciesielska, Artur Ludwin, Maciej W. W. Socha, Klaudia Skrzypek
Summary: Endometrial cancer, a common cancer in females, requires more efficient methods to determine malignancy and optimize treatment. The study aimed to evaluate the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. The levels of WNT-1 and mTOR in different cellular compartments were assessed in 64 patients with endometrial cancer of varying grades and stages. The results showed associations between WNT-1 and mTOR expression levels and tumor grade and staging, with membranous WNT-1 being negatively associated and cytoplasmic WNT-1 and nuclear mTOR being positively associated with higher grades of endometrial cancer, especially nuclear mTOR with FIGO stages IB-IV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Vicky Makker, Helen MacKay, Isabelle Ray-Coquard, Douglas A. Levine, Shannon N. Westin, Daisuke Aoki, Ana Oaknin
Summary: This comprehensive review provides updates on the epidemiology, pathophysiology, diagnosis, treatment, and patient quality-of-life considerations in the management of endometrial cancer. The Primer by Makker and colleagues summarizes the epidemiology, pathophysiology, diagnosis, treatment, and future research directions for endometrial cancer.
NATURE REVIEWS DISEASE PRIMERS
(2021)
Article
Oncology
Xinxing Pan, Zhe Geng, Jingyun Li, Xingxing Li, Mi Zhang, Xusu Wang, Yu Cong, Ke Huang, Juan Xu, Xuemei Jia
Summary: The study demonstrates that endogenous peptide PDHPS1 serves as an antitumor peptide by interacting with PTPA to inhibit the YAP signaling pathway in ovarian cancer development, showing no observable side effects on normal tissues.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Oxana V. Denisova, Joni Merisaari, Riikka Huhtaniemi, Xi Qiao, Laxman Yetukuri, Mikael Jumppanen, Amanpreet Kaur, Mirva Paakkonen, Carina von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Otto Kauko, Raphael Koch, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Mitochondrial glycolysis and hyperactivity of the AKT pathway are characteristic of brain tumors, but targeting AKT or PDK has shown limited clinical benefits. In this study, a triplet therapy targeting AKT, PDK, and PP2A was effective in inducing apoptosis in brain tumor cells. Reactivating PP2A converted the cytostatic response to cytotoxic apoptosis by shutting down compensatory mitochondrial oxidative phosphorylation. These findings suggest the potential of targeting mitochondrial metabolism to overcome therapy tolerance in brain tumors.
MOLECULAR ONCOLOGY
(2023)