- by Saito-Moriya, R., Iwano, S., Kitada, N., Yamasaki, N., Kamiya, G., Ogo, K., Sugiyama, T., Chuluun-Erdene, A., Isagawa, T., Obata, R., Ijuin, R., Abe, H., Kashiwakura, Y., Mabuchi, Y., Takahashi, M., Yamamoto, Y., Sawaki, D., Sato, T., Sato, S., Nishikii, H., Yoshimura, K., Hioki, H., Ohmori, T., Nakashiba, T., Hirano, T., Aoyama, H., Takeda, N., Miyawaki, A., Maki, S., Kuchimaru, T.Synthetic bioluminescence reactions exhibiting near-infrared (NIR)-shifted spectra have been explored to improve deep-tissue imaging through the design of firefly luciferin analogues. Although the NIR bioluminescence reactions improve the tissue penetration of bioluminescence signals from deep tissues, their photon output is markedly lower compared to the natural reaction with D-luciferin and firefly luciferase (Fluc), often by an order of magnitude or more. Consequently, in most instances, the sensitivity of NIR bioluminescence imaging (NIR-BLI) has not yet substantially surpassed that of BLI […]
- by Berens, E. B., Khou, S., Huang, E., Hoffman, A., Johnson, B., Kirchberger, N., Sivagnanam, S., Calistri, N. L., Derrick, D., Liby, T. A., McLean, I. C., Alanizi, A. A., Ozmen, F., Ozmen, T. Y., Mills, G. B., Hwang, E. S., Schedin, P. J., Gonzalez, H., Werb, Z., Heiser, L. M., Coussens, L. M.Dedifferentiation programs are commonly enacted during breast cancer progression to enable novel cellular phenotypes. Increased cellular plasticity within the neoplastic compartment of tumors correlates with disease aggressiveness, often culminating in greater resistance to cytotoxic therapies or the augmented ability to metastasize to distant organs. Here we report that subpopulations of dedifferentiated neoplastic breast epithelial cells express canonical leukocyte cell surface receptor proteins and have thus named this unique cellular program immune mimicry. We document neoplastic cells engaging in immune mimicry […]
- by Vital, M. F., Miranda, J. A., Carrolo, M., Quintela, A., Pinto, F. R.Background: Cancer is driven by the accumulation of somatic mutations, including driver mutations that confer a selective advantage to cancer cells. Driver proteins operate within complex interaction networks, and their activity is conditioned by neighbour proteins. Understanding the interplay between driver mutations and the expression of their neighbour proteins can provide insights into cancer biology and potential therapeutic targets. Methods: We assessed associations between expression of neighbour proteins and driver mutation status, comparing both between and within cancer types. We […]
- by Testa, S., Pal, A., Subramanian, A., Varma, S., Tang, J. P., Graham, D., Arfan, S., Pan, M., Bui, N. Q., Ganjoo, K. N., Dry, S., Huang, P. H., van de Rijn, M., Jiang, W., Kalbasi, A., Moding, E. J.The FDA approval of T cell receptor-engineered T cells (TCR-T) for synovial sarcoma demonstrates the potential for adoptive T cell therapies (ACTs) in solid tumors. However, the paucity of tumor-specific targets without expression in normal tissues remains a major bottleneck, especially in rare cancer subtypes. Here, we present a comprehensive computational pipeline called SCAN-ACT that leverages single cell RNA sequencing and multi-omics data from tumor and normal tissues to nominate and prioritize targets for both chimeric antigen receptor (CAR)- and […]
- by Cuesta, C., Alcon-Perez, M., Zheng, J., Procel, N., Cota, R. R., Fennema, D., Rosell, A., Meson, D. L., Martinez-Castedo, B., Arafat, Y., Sanz-Fraile, H., Rajeeve, V., Alonso, D., Hynds, R. E., Swanton, C., Alcaraz, J., Cutillas, P., Reyes-Aldasoro, C. C., Wang, H., Castellano, E.Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, promoting tumor progression through extracellular matrix (ECM) remodeling and paracrine signaling, but the signaling pathways controlling CAF function remain incompletely defined. Here, we demonstrate that RAS-PI3K signaling plays a central role in CAF activation and ECM remodeling by promoting collagen crosslinking, fibronectin organization, and glycoprotein deposition at least partially through the activation of YAP. Disruption of RAS-PI3K interaction in CAFs leads to structurally and mechanically defective ECMs that impair tumor […]
- by Parker, S.-A. J., Hough, A., Lax, N., Wright, T., Faruk, A., Fofie, C. K., Simcik, R., Cavanaugh, J. E., Kolber, B. J., Tidgewell, K. J.Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation of two new, veraguamide O (1) and veraguamide P (2), and one known, veraguamide C(3), analogs isolated from a cyanobacterial collection made in the Las Perlas Archipelago of Panama. We hypothesized that these compounds would be cytotoxic in cancer cell lines. The compounds were screened against HEK-293, estrogen receptor positive (MCF-7), and triple-negative breast cancer […]
- by Durfee, C., Bergstrom, E. N., Diaz-Gay, M., Zhou, Y., Temiz, N. A., Ibrahim, M. A., Nandi, S. P., Wang, Y., Liu, X., Steele, C. D., Proehl, J., Vogel, R. I., Argyris, P. P., Alexandrov, L. B., Harris, R.Mutations in somatic cells are inflicted by both extrinsic and intrinsic sources and contribute over time to cancer. Tobacco smoke contains chemical carcinogens that have been causatively implicated with cancers of the lung and head & neck. APOBEC family DNA cytosine deaminases have emerged as endogenous sources of mutation in cancer, with hallmark mutational signatures (SBS2/SBS13) that often co-occur in tumors of tobacco smokers with an equally diagnostic mutational signature (SBS4). Here we challenge the dogma that mutational processes are […]
- by Liu, F., Qian, J., Ma, C.Central Nervous System (CNS) tumors have sophisticated tumor microenvironment (TME) with different cell types such as astrocytes, microglia, neurons, vascular endothelial cells and immune cells. These non-cancerous cells orchestrate the brain TME to regulate cancer progression and therapeutic response. This study aimed to develop a cell composition deconvolution method for CNS tumor and to determine the impact of these cell compositions on patients outcomes. We identified the cell type-specific CpG loci using the pairwise differential methylation analysis for 13 major […]
- by Raza, Y., Moorthi, S., Yu, G., Chiappone, S., Vacchi-Suzzi, C., Luberto, C.Sphingomyelin Synthase 1 (gene name: SGMS1) participates in regulation of sphingolipid levels by synthesizing sphingomyelin from ceramide and phosphatidylcholine. Evidence have supported SGMS1's functions in regulating proliferation, cell cycle, cell death and migration. While its functions have begun to be explored, very little is known about upstream regulators. Here, we demonstrate that SGMS1 is a direct gene target of the GATA1-TAL1 transcriptional complex in K562 erythroleukemic cells. A predicted GATA1 consensus DNA binding sequence was identified with in a newly […]
- by Garcia, K. C., Khan, A. A., Ghosh, K., Sinha, S., Scalora, N., DeWane, G., Fullenkamp, C., Merritt, N., Drebot, Y., Yu, S., Leidinger, M., Henry, M. D., Breheny, P., Chimenti, M. S., Tanas, M. R.Purpose: Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has been challenging to target therapeutically. An integrated view of PI3K and Hippo pathway signaling is examined to determine if this could be leveraged therapeutically. Experimental design: A tissue microarray containing sarcomas of various histological types was evaluated for PTEN loss and correlated with levels of activated TAZ and […]
- by Steinbauer, S., Cowles, J. D., Sabbaghi, M. A., Poppelaars, M., Hussain, A., Wagesreither, M., Laimer-Gruber, D., Tovari, J., Szakacs, G., Csiszar, A.Triple-negative breast cancer (TNBC) is an aggressive form of cancer with poor prognosis. Beyond the absence of targeted therapies, a major challenge is its high recurrence rate, driven by the outgrowth of residual tumor cells that survive chemotherapy and persist during minimal residual disease (MRD). To monitor the therapy response of TNBC by enhanced intravital imaging, we established a clinically relevant combination chemotherapy protocol for the treatment of mouse mammary tumors engrafted from K14cre;Brca1F/F;Trp53F/F (KB1P) organoids engineered to express an […]
- by Zhao, H., Park, Y. M., Zheng, Y., Mao, Q., Collet, C. A., Hu, B., Zhou, T., Lin, L., Wong, S., Pan, Y., Monreal, A. V., Sinha, U. K., Sedghizadeh, P. P., Soragni, A., Lin, D.-C.Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity, which were further exacerbated by additional driver mutations (e.g., PIK3CA, NOTCH1, KMT2C). Single-cell analysis revealed an expansion of quiescent basal cells and proliferative squamous […]
- by Page, R., Martinez, O., Larcombe-Young, D., Bugallo-Blanco, E., Papa, S., Perucha, E.Cancer immunotherapy with engineered T cells has become a standard treatment for certain hematologic cancers. However, clinical trial outcomes for solid tumours are significantly lagging. A primary challenge in solid tumours is the lack of essential metabolites in the tumour microenvironment, such as glucose, due to poor vascularization and competition with tumour cells. To address this, we modified T cells to use fructose as an alternative energy source by introducing ectopic GLUT5 expression. We show that 'GLUT5-armored' T cells, engineered […]
- by Kung, C.-P., Terzich, N. D., Ilagan, M. X. G., Prinsen, M. J., Kaushal, M., Kladney, R. D., Weber, J. H., Mabry, A. R., Torres, L. S., Bramel, E. R., Freeman, E. C., Sabloak, T., Cottrell, K. A., Ryu, S., Weber, W. M., Maggi, L., Shriver, L. P., Patti, G. J., Weber, J. D.Triple-negative breast cancer (TNBC), lacking expression of estrogen, progesterone, and HER2 receptors, is aggressive and lacks targeted treatment options. An RNA editing enzyme, adenosine deaminase acting on RNA 1 (ADAR1), has been shown to play important roles in TNBC tumorigenesis. We posit that ADAR1 functions as a homeostatic factor protecting TNBC from internal and external pressure, including metabolic stress. We tested the hypothesis that the iron-dependent cell death pathway, ferroptosis, is a ADAR1-protected metabolic vulnerability in TNBC by showing that […]
- by Yue, M., Qin, Z., Tang, S., Cai, X., Zhao, Y., Chen, L., Chen, L., Ji, h.PIK3CA mutation is frequently concurrent with known oncogenic drivers such as EGFR mutation in lung cancer, raising an interesting question about its real function. Cachexia is a systemic disease involving complex interaction between primary tumors and distant organs, significantly contributing to cancer-related mortality. Through integrative study of genetically engineered mouse models (GEMMs) and clinical data, we find concurrent PIK3CA mutant preferentially drives cachexia in EGFR-mutant lung cancer, promoting malignant progression instead of cancer initiation. PIK3CA mutant-mediated cachexia could be overcome […]
- by Li, S., Xia, S., Lawas, M., Kulshreshtha, A., Garb, B. F., Perera, C., Li, C., Qin, T., Welch, J. D., DSilva, N. J., Rozek, L. S., Sartor, M. A.HPV integration (HPVint) is associated with carcinogenesis and tumor progression in HPV-associated cancers, including head and neck squamous cell carcinomas (HNSCC). While its impact on human DNA has been well characterized, its relationship with clinical outcomes remains unconfirmed. Here we investigate the consequences of HPVint both with respect to human and HPV characteristics by analyzing 261 HPV-associated HNSCC bulk and single-cell RNA-seq samples from five cohorts, and DNA HPVint events from 102 HPV+ participants in two of the cohorts. By […]
- by Sciacca, M., Carballo, M. d. P., Lacunza, E., Marino, L., Cardozo, P. N., Rodriguez Padilla, N., Lopez-Lopez, T., Abba, M., Courtois, L., Bieche, I., Vincent-Salomon, A., Bilbao, E. R., Podsypanina, K., Boissan, M., Chavrier, P., Eijan, A. M., Saez, P. J., Lodillinsky, C.Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor of invasive ductal carcinoma (IDC). The challenge lies in discriminating between DCIS progressors and DCIS non-progressors, often resulting in over- or under-treatment in many cases. Membrane type 1 (MT1)-matrix metalloproteinase (MMP) has been previously identified as an essential gene involved in DCIS progression. Here, RNA-sequencing analysis of MT1-MMPhigh subpopulation derived from invasive breast tumors in the intraductal xenograft model was compared against a dataset […]
- by Sekar, A., Chatterjee, R., Selvadurai, B. R., Ray, L., Verma, A., Nataraj, N. B., Garcia, D. D., Giri, S., Genna, A., Karatekin, F., Gupta, N., Zerbib, M., Vinik, Y., Avioz, T., Weizman, E., David, E., A. Schaffer, A., Pan, Y., Huang, H., M van Weerden, W., Corey, E., Hunt, H., Greenstein, A., Blecher-Gonen, R., Oren, R., Afek, A., Amit, I., Lev, S., Ku, A., Kartal, S., R. Bright, J., T. Lis, R., L. Dahut, W., Sowalsky, A. G., Ruppin, E., Yarden, Y.Approximately 50% of prostate cancer (PCa) patients harbor fusions involving the TMPRSS2 and ERG genes. Despite this, tailored therapies targeting the fused gene, tERG, remain undeveloped. Our study analyzed biopsy samples from two clinical trials assessing the efficacies of androgen receptor (AR) signaling inhibitors (ARSIs). The results revealed that tERG promotes resistance to ARSIs and is associated with elevated levels of the glucocorticoid receptor (GR). Subsequent assays showed that GR directly interacts with tERG, alleviates allosteric autoinhibition and prevents chemotherapy-induced […]
- by Khan, M. M., Roos, W. P., Angajala, A., Gibbs, D. Y., Liu, J. C., Ragin, C., Sobol, R. W.Head and Neck Squamous Cell Carcinoma (HNSCC) imposes a significant health burden, necessitating innovative therapeutic strategies to enhance treatment efficacy. Current treatments such as surgery, radiation, and chemotherapy have limited effectiveness and yield severe side effects, emphasizing the need for targeted therapies. We have focused on DNA polymerase beta (Pol{beta}) and its roles in replication stress, cellular responses to DNA damaging therapies, and DNA damage response modifiers. Our investigations reveal a regulatory role for base excision repair (BER) proteins, including […]
- by Linares-Blanco, J., Chicote, I., Ros, J., Alcantara, A. M., Martinez-Quintanilla, J., Elez, E., Palmer, H. G., Fernandez-Lozano, C., Seoane, J. A.Colon cancer is the second most common cause of cancer death worldwide. Despite advances in the development of new molecular strategies for stratifying patients with colon cancer, many of these patients do not respond adequately to the standard of care. While previous studies have focused on the development of prognostic gene expression signatures, the exploration of predictive signatures to inform treatment decisions remains incomplete. In this study, we leveraged public gene expression datasets to design and experimentally validate a 37-gene […]
Mass spectrometry websites, social media, journal feeds, and other links and items of interest to the mass spectrometry community.
