Article
Cell Biology
Jenna M. Giafaglione, Preston D. Crowell, Amelie M. L. Delcourt, Takao Hashimoto, Sung Min Ha, Aishwarya Atmakuri, Nicholas M. Nunley, Rachel M. A. Dang, Mao Tian, Johnny A. Diaz, Elisavet Tika, Marie C. Payne, Deborah L. Burkhart, Dapei Li, Nora M. Navone, Eva Corey, Peter S. Nelson, Neil Y. C. Lin, Cedric Blanpain, Leigh Ellis, Paul C. Boutros, Andrew S. Goldstein
Summary: This study reveals the differences in metabolism and nutrient utilization between basal and luminal cells in prostate epithelium, as well as the increased pyruvate oxidation during basal-to-luminal differentiation. The researchers identify the mitochondrial pyruvate carrier and lactate accumulation as crucial regulators of prostate epithelial lineage identity.
NATURE CELL BIOLOGY
(2023)
Article
Oncology
Undraga Schagdarsurengin, Vanessa Breiding, Maria Loose, Florian Wagenlehner, Temuujin Dansranjav
Summary: The overexpression of IRAK1 in prostate cancer is associated with resistance to radiation-induced tumor cell death. The expression of IRAK1 is correlated with the methylation status of tumor cells, making it a potential predictive marker for selective IRAK1-targeting therapies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Sherly I. Celada, Guoliang Li, Lindsay J. Celada, Wenfu Lu, Thanigaivelan Kanagasabai, Weiran Feng, Zhen Cao, Nazifa Salsabeel, Ninghui Mao, LaKendria K. Brown, Zaniya A. Mark, Michael G. Izban, Billy R. Ballard, Xinchun Zhou, Samuel E. Adunyah, Robert J. Matusik, Xiaofei Wang, Zhenbang Chen
Summary: Changes in FOXA1 protein levels are associated with prostate cancer progression. We found that SKP2 catalyzes the degradation of FOXA1 through polyubiquitination, and the SKP2:FOXA1 protein ratio increases during PCa progression. The SKP2-FOXA1 interplay plays a significant role in PCa.
MOLECULAR ONCOLOGY
(2023)
Article
Cell Biology
Yueli Liu, Jiawen Wang, Corrigan Horton, Chuan Yu, Beatrice Knudsen, Joshua Stefanson, Kevin Hu, Ofir Stefanson, Jonathan Green, Charlene Guo, Qing Xie, Zhu A. Wang
Summary: This study reveals that stromal AR inhibits prostate cancer progression by restraining secretory luminal cells, and deletion of stromal AR exacerbates tumor progression and leads to changes in the cellular state of secretory luminal cells.
Article
Pharmacology & Pharmacy
Tzu-Hung Hsiao, Ren Ching Wang, Tsai-Jung Lu, Chien-Hung Shih, Yu-Chen Su, Jia-Rong Tsai, Pei-Pei Jhan, Cai-Sian Lia, Han-Ni Chuang, Kuang-Hsi Chang, Chieh-Lin Teng
Summary: In patients with de novo acute myeloid leukemia (AML), higher levels of Myc gene expression were associated with poor response to the 7 + 3 induction regimen. However, c-Myc protein expression, particularly c-Myc-immunopositivity, could serve as a surrogate marker for predicting the response to 7 + 3 induction chemotherapy. Additionally, c-Myc-immunopositivity improved the specificity of cytogenetics in predicting the chemoresponse to 7 + 3 induction.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Juntae Kwon, Jinmin Zhang, Boram Mok, Samuel Allsup, Chul Kim, Jeffrey Toretsky, Cecil Han
Summary: This study established a mouse model of LUSC and found that USP13 is a molecular driver of lineage plasticity in club cells and is associated with upregulation of squamous programs in lung cancer cells.
Article
Cell Biology
Zhenghao Yang, Xiaochan Xu, Chan Gu, Alexander Valentin Nielsen, Guokai Chen, Fan Guo, Chao Tang, Yang Zhao
Summary: In this study, researchers discovered a plastic chemically activated multi-lineage priming (CaMP) state at the beginning of chemical reprogramming. This state enhances the cells' potential to adapt to other cell fates. By introducing this plastic state, the efficiency of chemical reprogramming from fibroblasts to functional neuron-like cells or skeletal muscles was significantly improved, bypassing the need for inducing pluripotent stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Alison M. Ferguson, Mark A. Rubin
Summary: The emergence of small cell prostate cancer is associated with tumor cell plasticity and evasion of environmental pressures. In-depth understanding of tumor plasticity can be achieved through clinical cohorts and disease progression models. Studying the tumor microenvironment and earlier time points can provide a comprehensive understanding and potentially lead to better patient outcomes by intervening early to reverse plasticity and prevent transition to the aggressive small cell phenotype.
Article
Cell Biology
Alastair Davies, Shaghayegh Nouruzi, Dwaipayan Ganguli, Takeshi Namekawa, Daksh Thaper, Simon Linder, Fatih Karaoglanoglu, Meltem E. Omur, Soojin Kim, Maxim Kobelev, Sahil Kumar, Olena Sivak, Chiara Bostock, Jennifer Bishop, Marlous Hoogstraat, Amina Talal, Suzan Stelloo, Henk van der Poel, Andries M. Bergman, Musaddeque Ahmed, Ladan Fazli, Haojie Huang, Wayne Tilley, David Goodrich, Felix Y. Feng, Martin Gleave, Housheng Hansen He, Faraz Hach, Wilbert Zwart, Himisha Beltran, Luke Selth, Amina Zoubeidi
Summary: The study demonstrates that prostate cancer can transition to a high-plasticity state in response to potent androgen receptor antagonism, maintaining AR activity and rerouting transcriptional activity through changes in chromatin architecture. This reprogramming is mediated by EZH2 and favors stem cell and neuronal gene networks, highlighting the potential for reversing treatment resistance in prostate cancer.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Xiaoqi Han, Siyuan Jiang, Yinmin Gu, Lihua Ding, Enhao Zhao, Dongxing Cao, Xiaodong Wang, Ya Wen, Yongbo Pan, Xin Yan, Liqiang Duan, Minxuan Sun, Tao Zhou, Yajuan Liu, Hongbo Hu, Qinong Ye, Shan Gao
Summary: In this study, it was found that HUNK inhibits EMT and metastasis of CRC cells through its kinase-dependent interaction with GEF-H1. HUNK directly phosphorylates GEF-H1 at serine 645, leading to activation of RhoA and subsequent phosphorylation of LIMK-1/CFL-1, resulting in stabilization of F-actin and inhibition of EMT. Clinically, decreased levels of HUNK expression and phosphorylation of GEF-H1 at serine 645 were observed in CRC tissues with metastasis, indicating their potential as biomarkers for metastasis.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Lee Armstrong, Colin E. Willoughby, Declan J. Mckenna
Summary: This study investigated the association between miR-143-3p and EMT in prostate cancer. The findings showed that miR-143-3p expression was significantly decreased in prostate cancer cells and it was associated with the EMT-associated gene AKT1. Further analysis suggested that miR-143-3p may serve as a predictor of disease recurrence in prostate cancer, making it a potential diagnostic and prognostic biomarker.
Article
Biochemistry & Molecular Biology
Jitender Monga, Indra Adrianto, Craig Rogers, Shirish Gadgeel, Dhananjay Chitale, Joshi J. Alumkal, Himisha Beltran, Amina Zoubeidi, Jagadananda Ghosh
Summary: This study demonstrates that TRIB2 is overexpressed in enzalutamide-resistant prostate cancer cells and tumors. Inhibition of TRIB2 decreases the viability of enzalutamide-resistant prostate cancer cells, while overexpression of TRIB2 confers resistance to clinically relevant doses of enzalutamide. TRIB2 downregulates luminal markers and upregulates neuronal markers in prostate cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Endocrinology & Metabolism
William K. Storck, Allison M. May, Thomas C. Westbrook, Zhi Duan, Colm Morrissey, Joel A. Yates, Joshi J. Alumkal
Summary: The androgen receptor (AR) signaling pathway plays a critical role in the growth and differentiation of prostate cancer cells. Androgen deprivation therapy is the main treatment for metastatic prostate cancer, but resistance to AR signaling inhibitors is common. Lineage plasticity, specifically the switch to an alternate differentiation program, is a recently identified resistance mechanism. This review discusses the role of AR pathway loss and activation of a neuronal differentiation program in lineage plasticity, and explores new epigenetic therapeutic strategies to reverse this process.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Oh-Joon Kwon, Li Zhang, Deyong Jia, Li Xin
Summary: Sox2 plays a crucial role in the neuroendocrine differentiation of prostate adenocarcinoma. Both Sca-1(+) and Sca-1(-) luminal cells in the mouse prostate are susceptible to oncogenic transformation induced by Pten loss. Tumors derived from Sca-1(+) cells show resistance to castration and are more likely to undergo castration-induced neuroendocrine differentiation.
Article
Environmental Sciences
Wonhyoung Park, Sunwoo Park, Whasun Lim, Gwonhwa Song
Summary: Research results indicate that bifenthrin inhibits cell proliferation and viability, induces cell cycle arrest and apoptosis in both porcine trophectoderm and uterine luminal epithelial cells. Bifenthrin also damages mitochondria, induces reactive oxygen species production, leading to endoplasmic reticulum stress and calcium dysregulation in the cells. Finally, bifenthrin alters MAPK/PI3K signaling pathway and expression of pregnancy-related genes.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Cell & Tissue Engineering
Oh-Joon Kwon, Jong Min Choi, Li Zhang, Deyong Jia, Zhouyihan Li, Yiqun Zhang, Sung Yun Jung, Chad J. Creighton, Li Xin
Editorial Material
Cell Biology
Li Xin
Summary: EZH2 has been shown to promote the development of castration-resistant prostate cancer (CRPC) by interacting with the androgen receptor (AR) to reprogram its transcriptional activity, facilitating the transition of CRPC into a lineage infidelity state.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Oh-Joon Kwon, Boyu Zhang, Deyong Jia, Li Zhang, Xing Wei, Zhicheng Zhou, Deli Liu, Khoi Trung Huynh, Kai Zhang, Yiqun Zhang, Paul Labhart, Andrea Sboner, Chris Barbieri, Michael C. Haffner, Chad J. Creighton, Li Xin
Summary: Macrophages are increased in both benign prostatic hyperplasia and prostate cancer. Using a Pb-Csf1 mouse model, the overexpression of macrophage colony-stimulating factor (Csf1) is found to promote immune cell infiltration into the prostate, modulate macrophage polarity, and induce prostate intraepithelial neoplasia (PIN). These findings are similar to the transcriptional alterations observed in human prostate cancer patients with high CSF-1 expression.
Article
Multidisciplinary Sciences
Deyong Jia, Zhicheng Zhou, Oh-Joon Kwon, Li Zhang, Xing Wei, Yiqun Zhang, Mingyang Yi, Martine P. Roudier, Mary C. Regier, Ruth Dumpit, Peter S. Nelson, Mark Headley, Lawrence True, Daniel W. Lin, Colm Morrissey, Chad J. Creighton, Li Xin
Summary: Increasing prostatic stromal Foxf2 can suppress the growth and progression of prostate cancer by attenuating the immunosuppressive effect of cancer-associated fibroblasts and enhancing T cell cytotoxicity. The expression level of FOXF2 in human prostate has an inverse correlation with the development of cancer.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Cell Biology
Li Xin
Summary: A recent study by Steiner et al. reveals that Ly6d(+) prostate tumor cells can survive after castration through an autocrine amphiregulin signaling pathway.
TRENDS IN CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhicheng Zhou, Deyong Jia, Ohjoon Kwon, Shan Li, Huiyun Sun, Martine P. Roudier, Daniel W. W. Lin, Lawrence True, Colm Morrissey, Chad J. Creighton, John K. K. Lee, Li Xin
Summary: The complement system, through the membrane attack complex (MAC), plays a critical role in the innate immune response. Complement component 7 (C7) is important for MAC assembly and its expression level affects cytolytic activity. Our research demonstrates that C7 is specifically expressed by stromal cells in the prostate and its levels are inversely correlated with clinical outcomes in prostate cancer. Androgen signaling positively regulates C7 expression and replenishing C7 suppresses tumor growth, suggesting that enhancing complement activity could be a potential therapeutic approach.
Article
Biochemistry & Molecular Biology
Oh-Joon Kwon, Li Zhang, Deyong Jia, Li Xin
Summary: Sox2 plays a crucial role in the neuroendocrine differentiation of prostate adenocarcinoma. Both Sca-1(+) and Sca-1(-) luminal cells in the mouse prostate are susceptible to oncogenic transformation induced by Pten loss. Tumors derived from Sca-1(+) cells show resistance to castration and are more likely to undergo castration-induced neuroendocrine differentiation.