Article
Oncology
Emilly S. Villodre, Xiaoding Hu, Richard Larson, Pascal Finetti, Kristen Gomez, Wintana Balema, Shane R. Stecklein, Ginette Santiago-Sanchez, Savitri Krishnamurthy, Juhee Song, Xiaoping Su, Naoto T. Ueno, Debu Tripathy, Steven Van Laere, Francois Bertucci, Pablo Vivas-Mejia, Wendy A. Woodward, Bisrat G. Debeb
Summary: The study found that lipocalin 2 (LCN2) is expressed at significantly higher levels in inflammatory breast cancer (IBC) and is associated with poor prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 can inhibit aggressive behavior of IBC cells in vivo and suppress tumor growth and invasion in mouse models of IBC. Analysis of proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells, indicating LCN2 promotes IBC tumor aggressiveness and could be a potential therapeutic target for IBC.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Gabriela Ortiz-Soto, Natalia S. Babilonia-Diaz, Mercedes Y. Lacourt-Ventura, Delmarie M. Rivera-Rodriguez, Jailenne I. Quinones-Rodriguez, Monica Colon-Vargas, Israel Almodovar-Rivera, Luis E. Ferrer-Torres, Ivette J. Suarez-Arroyo, Michelle M. Martinez-Montemayor
Summary: Inflammatory breast cancer (IBC) is a lethal subtype of breast cancer, comprising 1-5% of all cases. This study confirms the overexpression of metadherin (MTDH) in IBC cells and reveals its crucial role in IBC progression, including signaling pathway regulation and tumor growth promotion. CRISPR/Cas9 editing of IBC cells shows that the absence of MTDH significantly reduces cell migration, proliferation, and tumor spheroid formation, as well as the expression of key signaling molecules in IBC. Additionally, IBC xenografts exhibit distinct tumor growth patterns and phenotypes in lung tissue. These findings highlight MTDH as a potential therapeutic target for IBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Bin Shen, Yang Li, Qian Ye, Youyou Qin
Summary: Triple-negative breast cancer (TNBC) is an aggressive cancer associated with poor overall survival. This study revealed that upregulation of YY1 and lncRNA Kcnq1ot1 in TNBC tissues was correlated with worse patient survival. Mechanistically, YY1 was found to upregulate lncRNA Kcnq1ot1, which decreased PTEN expression via methylation, leading to increased TNBC cell proliferation and invasion. In vivo models further confirmed the tumorigenic effects of YY1, lncRNA Kcnq1ot1, and PTEN in TNBC.
CANCER GENE THERAPY
(2021)
Article
Oncology
Caroline Schreiber, Annette Gruber, Sven Rosswag, Supriya Saraswati, Shannon Harkins, Wilko Thiele, Natalie Munding, Anja Schmaus, Melanie Rothley, Arno Dimmler, Motomu Tanaka, Boyan K. K. Garvalov, Jonathan P. P. Sleeman, Zahra Hajian Foroushani
Summary: ASAP1 is a multi-domain adaptor protein that regulates cytoskeletal dynamics and tumor cell migration. Our study reveals a tumor suppressive role for ASAP1 in breast cancer, as its deletion accelerates tumor initiation and metastasis.
Article
Cell Biology
Fangzhou Ye, Yiran Liang, Yajie Wang, Robert Le Yang, Dan Luo, Yaming Li, Yuhan Jin, Dianwen Han, Bing Chen, Wenjing Zhao, Lijuan Wang, Xi Chen, Tingting Ma, Xiaoli Kong, Qifeng Yang
Summary: Breast cancer is a common malignancy and exosome-mediated communication between cancer-associated fibroblasts (CAFs) and breast cancer cells plays a role in tumor progression. This study identified circTBPL1 as an upregulated circRNA in exosomes derived from CAFs. Transfer of exosomal circTBPL1 from CAFs to breast cancer cells promoted cell proliferation, migration, and invasion. Further investigation revealed that circTBPL1 acts as a sponge for miR-653-5p, leading to increased expression of TPBG and enhanced breast cancer progression. These findings suggest that exosomal circTBPL1 could serve as a biomarker and therapeutic target for breast cancer.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Liantao Guo, Faminzi Li, Hanqing Liu, Deguang Kong, Chuang Chen, Shengrong Sun
Summary: Our study investigates the role and mechanism of SIX1 upregulation in breast cancer carcinogenesis. We found that SIX1 expression varies among different subtypes of breast cancer and that it upregulates breast cancer grading and lymph node metastasis. Additionally, SIX1 participates in the rewiring of several cancer signaling pathways and interacts with cancer stem cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ragini Yeeravalli, Komal Kaushik, Amitava Das
Summary: The study demonstrates the crucial role of PDGFR beta in regulating EMT in breast CSCs, leading to increased physiological and molecular properties in breast cancer cells and CSCs with PDGFR beta overexpression. Mechanistically, PDGFR beta overexpression induces FAK and Src activation, promoting cell migration and invasion. Stable silencing of PDGFR beta disrupts these biological phenomena and could be a potential therapeutic target for treating TNBC patients.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Lijuan Guo, Wanjun Zhang, Xue Zhang, Jun Wang, Jiaqi Nie, Xiaomeng Jin, Ying Ma, Shi Wang, Xinhong Zhou, Yilei Zhang, Yan Xu, Yoshimasa Tanaka, Jingping Yuan, Xing-Hua Liao, Yiping Gong, Li Su
Summary: In this study, SIPA1 was found to function as a transcription factor that regulates the expression of genes involved in cell growth, differentiation, and response to environmental factors. Importin β1 was identified as an interacting partner of SIPA1 during fibronectin treatment. SIPA1's DNA-binding region (DBR) recognized and bound to a TGAGTCAB motif, and its transcriptional regulation was shown to be necessary for the migration and invasion of triple-negative breast cancer cells.
Article
Oncology
Jiamin Zhou, Xianglin Sun, Xinyu Zhang, Huan Yang, Zhenglin Jiang, Qianqian Luo, Yifei Liu, Guohua Wang
Summary: miR-107 potentially regulates NEDD9 expression and affects invasion, migration, and proliferation of breast cancer cells. Overexpression of miR-107 suppresses NEDD9 expression and inhibits cell invasion and metastasis, while interference with miR-107 promotes NEDD9 expression and enhances invasion and metastasis.
Article
Oncology
Jing Chen, Jingjing Sun, Qunfeng Wang, Yanze Du, Jie Cheng, Juan Yi, Bei Xie, Suya Jin, Gang Chen, Lina Wang, Xiaoyuan Wang, Hulai Wei
Summary: Functional loss or deletion of the tumor suppressor gene PTEN significantly enhances the proliferation, invasion, and metastasis of breast cancer cells. Inhibition of PTEN in the overall microenvironment also promotes the proliferation and metastasis of breast cancer cells. These findings suggest that PTEN mediates the proliferation, invasion, and metastasis of mouse breast cancer cells by regulating the PI3K-Akt signaling pathway.
FRONTIERS IN ONCOLOGY
(2022)
Article
Physics, Multidisciplinary
Kijung Kim, Jinseung Choung, Ung Hyun Ko, Ara Jung, Wonho Choe, Jennifer H. Shin, Bomi Gweon
Summary: Atmospheric pressure plasma (APP) has emerged as a potent tool for cancer therapy due to its various anti-cancer effects, including altering cancer cell morphology, suppressing migratory activity, and reducing invasiveness. By down-regulating markers associated with epithelial to mesenchymal transition (EMT), APP treatment may have the potential to suppress cancer metastasis.
FRONTIERS IN PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Ran Sun, Jin He, Qin Xiang, Yixiao Feng, Yijia Gong, Yijiao Ning, Chaoqun Deng, Kexin Sun, Mingjun Zhang, Zhaobo Cheng, Xin Le, Qi Xiong, Fengsheng Dai, Yongzhong Wu, Tingxiu Xiang
Summary: Breast cancer metastasis can occur even with a small primary tumor. Neurotrophin 4 (NTF4) has been found to play a dual role in breast cancer by promoting proliferation and metastasis. High levels of NTF4, especially in early stages, are associated with poor clinical outcomes, emphasizing the importance of metastasis in breast cancer mortality. Mechanistically, NTF4 activates specific pathways to promote epithelial-mesenchymal transition and cell motility, while inhibiting cell proliferation and promoting apoptosis. These findings suggest that NTF4 could be a prognostic marker and potential therapeutic target for breast cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Christoforos Thomas, Ilias Karagounis, Ratnesh K. Srivastava, Nicholas Vrettos, Fotis Nikolos, Noelle Francois, Menggui Huang, Siliang Gong, Qi Long, Sushil Kumar, Constantinos Koumenis, Savitri Krishnamurthy, Naoto T. Ueno, Rumela Chakrabarti, Amit Maity
Summary: Studies have shown that in inflammatory breast cancer, ERβ can act as a tumor suppressor by inhibiting cell migration and reducing metastasis.
Article
Oncology
Haruko Hayasaka, Junichi Yoshida, Yasutaka Kuroda, Akihiro Nishiguchi, Michiya Matsusaki, Kei Kishimoto, Hitoshi Nishimura, Mari Okada, Yuki Shimomura, Daichi Kobayashi, Yoshihito Shimazu, Yuji Taya, Mitsuru Akashi, Masayuki Miyasaka
Summary: Chemokines play a crucial role in breast cancer metastasis to lymph nodes, with the CXCL12/CXCR4 signaling pathway promoting breast cancer cell migration towards CCR7 ligand-expressing intratumoral lymphatic vessels.
Article
Cell Biology
Jie Wang, Zhiwei He, Xinyuan Liu, Jian Xu, Xueyi Jiang, Gang Quan, Jianxin Jiang
Summary: This study demonstrates the mechanism of LINC00941 in pancreatic cancer and reveals its role in promoting proliferation and metastasis through binding to ANXA2 and increasing its stability.
CELL DEATH & DISEASE
(2022)
Review
Pharmacology & Pharmacy
Xuemei Xie, Jangsoon Lee, Toshiaki Iwase, Megumi Kai, Naoto T. Ueno
Summary: This narrative review discusses emerging targets for TNBC treatment, challenges in their identification and validation, and future research directions. Overcoming these challenges requires the application of novel technologies and combination therapy for effective disease control.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Multidisciplinary Sciences
Lucia Ruojia Wu, Peng Dai, Michael Xiangjiang Wang, Sherry Xi Chen, Evan N. Cohen, Gitanjali Jayachandran, Jinny Xuemeng Zhang, Angela Serrano, Nina Guanyi Xie, Naoto T. Ueno, James M. Reuben, Carlos H. Barcenas, David Yu Zhang
Summary: The authors report a PCR-based molecular barcoding sequencing method called quantitative amplicon sequencing (QASeq), which allows accurate and sensitive quantification of nucleic acids. Compared to traditional droplet digital PCR, QASeq exhibits higher and more consistent conversion yield in molecule count quantitation. Multiplexing with QASeq improves the sensitivity of detecting copy number variation (CNV).
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Nour Abuhadra, Ryan Sun, Jennifer K. Litton, Gaiane M. Rauch, Clinton Yam, Jeffrey T. Chang, Sahil Seth, Roland Bassett, Bora Lim, Alastair M. Thompson, Elizabeth Mittendorf, Beatriz E. Adrada, Senthil Damodaran, Jason White, Elizabeth Ravenberg, Rosalind Candelaria, Banu Arun, Naoto T. Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K. Murthy, Nuhad Ibrahim, Aysegul A. Sahin, Vicente Valero, William Fraser Symmans, Debu Tripathy, Stacy Moulder, Lei Huo
Summary: In TNBC patients without a complete pathologic response, high baseline stromal tumor-infiltrating lymphocytes (sTILs) did not show a significant association with event-free survival (EFS), suggesting that sTILs may not confer a benefit in EFS in the absence of a pCR. RNA-seq analysis revealed more CD8+ T cells in the high-sTIL group with favorable EFS, indicating lymphocyte type may be an important parameter for de-escalation strategies. Further research is needed to investigate the implications of these findings in the context of immune checkpoint inhibitor therapy.
Article
Oncology
Maitri Kalra, Elizabeth Henry, Kelly McCann, Meghan S. Karuturi, Jean G. Bustamante Alvarez, Amanda Parkes, Robert Wesolowski, Mei Wei, Sarah S. Mougalian, Gregory Durm, Angel Qin, Caitlin Schonewolf, Meghna Trivedi, Avan J. Armaghani, Frederick H. Wilson, Wade T. Iams, Anita A. Turk, Praveen Vikas, Michael Cecchini, Sam Lubner, Priyadarshini Pathak, Kristen Spencer, Vadim S. Koshkin, Matthew K. Labriola, Catherine H. Marshall, Katy E. Beckermann, Marina N. Sharifi, Anthony C. Bejjani, Varsha Hotchandani, Samir Housri, Nadine Housri
Summary: Academics from National Cancer Institute-designated Comprehensive Cancer Centers in the United States share expert knowledge with oncologists across the country through an online Q&A platform, significantly impacting clinical practices, improving patient care, and providing a source of new knowledge and education in the field of oncology.
Article
Oncology
Adrienne N. Cobb, Kevin Diao, Mediget Teshome, Anthony Lucci, Naoto T. Ueno, Michael Stauder, Rachel M. Layman, Henry M. Kuerer, Wendy A. Woodward, Susie X. Sun
Summary: This study evaluated the long-term outcomes of patients with inflammatory breast cancer (IBC) and N3c disease and found that patients with IBC and supraclavicular nodal involvement experience excellent locoregional control and favorable survival with comprehensive trimodality therapy and a multidisciplinary team approach.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Clara R. Farley, Shelby Irwin, Taiwo Adesoye, Susie X. Sun, Sarah M. DeSnyder, Anthony Lucci, Simona F. Shaitelman, Edward Chang, Naoto T. Ueno, Wendy A. Woodward, Mediget Teshome
Summary: BCRL is a common complication in IBC patients and strategies should be implemented to reduce or prevent its occurrence and improve real-time diagnosis for early management in this population.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Summer Y. Y. Ha, Yasuaki Anami, Chisato M. Yamazaki, Wei Xiong, Candice M. Haase, Scott D. Olson, Jangsoon Lee, Naoto T. Ueno, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama
Summary: The glutamic acid-glycine-citrulline (EGCit) linker has been found to address the stability issues of Valine-citrulline linker in drug delivery, without compromising drug release and ADC therapeutic efficacy. EGCit conjugates resist degradation by neutrophil proteases and show potent antitumor activity with minimal blood and liver toxicity.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Medicine, General & Internal
Shanu Modi, William Jacot, Toshinari Yamashita, Joohyuk Sohn, Maria Vidal, Eriko Tokunaga, Junji Tsurutani, Naoto T. Ueno, Aleix Prat, Yee Soo Chae, Keun Seok Lee, Naoki Niikura, Yeon Hee Park, Binghe Xu, Xiaojia Wang, Miguel Gil-Gil, Wei Li, Jean-Yves Pierga, Seock-Ah Im, Halle C. F. Moore, Hope S. Rugo, Rinat Yerushalmi, Flora Zagouri, Andrea Gombos, Sung-Bae Kim, Qiang Liu, Ting Luo, Cristina Saura, Peter Schmid, Tao Sun, Dhiraj Gambhire, Lotus Yung, Yibin Wang, Jasmeet Singh, Patrik Vitazka, Gerold Meinhardt, Nadia Harbeck, David A. Cameron
Summary: Trastuzumab deruxtecan demonstrated significantly longer progression-free and overall survival compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Correction
Oncology
Fei Su, Xiaoping Wang, Troy Pearson, Jangsoon Lee, Savitri Krishnamurthy, Naoto T. Ueno, Mikhail G. Kolonin
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Editorial Material
Oncology
Adrienne N. Cobb, Kevin Diao, Mediget Teshome, Anthony Lucci, Naoto T. Ueno, Michael Stauder, Rachel M. Layman, Henry M. Kuerer, Wendy A. Woodward, Susie X. Sun
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Francois Richard, Maxim De Schepper, Marion Maetens, Sophia Leduc, Edoardo Isnaldi, Tatjana Geukens, Karen Van Baelen, Ha-Linh Nguyen, Peter Vermeulen, Steven Van Laere, Francois Bertucci, Naoto Ueno, Luc Dirix, Giuseppe Floris, Elia Biganzoli, Christine Desmedt
Summary: In this study, the genomic alterations in primary and metastatic tumor samples from patients with metastatic inflammatory breast cancer (IBC) and non-IBC were compared. Higher frequency of AURKA amplification was observed in IBC, which was associated with increased AURKA mRNA expression and worse prognosis. These findings should be further investigated considering the existence of AURKA inhibitors.
Article
Oncology
Nour Abuhadra, Ryan Sun, Clinton Yam, Gaiane M. Rauch, Qingqing Ding, Bora Lim, Alastair M. Thompson, Elizabeth A. Mittendorf, Beatriz E. Adrada, Senthil Damodaran, Kiran Virani, Jason White, Elizabeth Ravenberg, Jia Sun, Jaihee Choi, Rosalind Candelaria, Banu Arun, Naoto T. Ueno, Lumarie Santiago, Sadia Saleem, Sausan Abouharb, Rashmi K. Murthy, Nuhad Ibrahim, Aysegul Sahin, Vicente Valero, William Fraser Symmans, Jennifer K. Litton, Debu Tripathy, Stacy Moulder, Lei Huo
Summary: In this study, clinicopathologic features, including sTILs, Ki-67, PD-L1, and androgen receptor, were evaluated in 408 early-stage TNBC patients. Integrating high Ki-67 (>35%) and high sTILs (≥20%) in a computed response score model predicted a pCR rate of 65%. This model has the potential to refine patient selection for neoadjuvant clinical trials evaluating de-escalation strategies.
Article
Oncology
Evan N. Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B. McBride, Franklin D. Alvarez, Megumi Kai, Juhee Song, Yu Shen, Jie S. Willey, Bora Lim, Vicente Valero, Naoto T. Ueno, James M. Reuben
Summary: Circulating tumor cells (CTCs) are valuable indicators for managing metastatic breast cancer (MBC). Enrichment of CTCs based on size and deformability can capture a wider range of tumor cells, providing a complementary approach to tissue biopsy. A longitudinal study using a microcavity array showed that the shift from epithelial CTCs to those with a mesenchymal expression pattern is associated with worse clinical outcomes.
Article
Biochemistry & Molecular Biology
Xuemei Xie, Jangsoon Lee, Jon A. Fuson, Huey Liu, Toshiaki Iwase, Kyuson Yun, Cori Margain, Debu Tripathy, Naoto T. Ueno
Summary: In this study, RNAi screening and pathway analysis identified 135 potential kinase targets whose inhibition enhanced the antiproliferation effect of eribulin in TNBC cells. The PI3K/Akt/mTOR and MAPK/JNK pathways emerged as the top candidates. Combination of eribulin with copanlisib, everolimus, trametinib, and JNK-IN-8 produced strong synergistic antiproliferative effects, with the PI3K and mTOR inhibitors showing the most potent effects in vitro.
Article
Oncology
Hiroko Masuda, Kenichi Harano, Sakiko Miura, Ying Wang, Yuko Hirota, Oi Harada, Mohit Kumar Jolly, Yuki Matsunaga, Bora Lim, Anita L. Wood, Napa Parinyanitikul, Hee Jin Lee, Gyungyub Gong, Jason T. George, Herbert Levine, Jangsoon Lee, Xiaoping Wang, Anthony Lucci, Arvind Rao, Brock L. Schweitzer, O. Rayne Lawrence, Robert S. Seitz, Stephan W. Morris, David R. Hout, Seigo Nakamura, Savitri Krishnamurthy, Naoto T. Ueno
Summary: The study found that TNBC molecular subtype and IM signature frequently change after NST, and the results suggest that EMT is promoted in the changed subtypes.
JCO PRECISION ONCOLOGY
(2022)