Deubiquitinase OTUD6B Isoforms Are Important Regulators of Growth and Proliferation
Deubiquitinases (DUB) are increasingly linked to the regulation of fundamental processes in normal and cancer cells, including DNA replication and repair, programmed cell death, and oncogenes and tumor suppressor signaling. Here, evidence is presented that the deubiquitinase OTUD6B regulates protein synthesis in non–small cell lung cancer (NSCLC) cells, operating downstream from mTORC1. OTUD6B associates with the protein synthesis initiation complex and modifies components of the 48S preinitiation complex. The two main OTUD6B splicing isoforms seem to regulate protein synthesis in opposing fashions: the long OTUD6B-1...
Source: Molecular Cancer Research - January 30, 2017 Category: Cancer & Oncology Authors: Sobol, A., Askonas, C., Alani, S., Weber, M. J., Ananthanarayanan, V., Osipo, C., Bocchetta, M. Tags: Cell Cycle and Senescence Source Type: research
Highlights of This Issue
(Source: Molecular Cancer Research)
Source: Molecular Cancer Research - January 30, 2017 Category: Cancer & Oncology Tags: Highlights Source Type: research
Overcoming EGFR Bypass Signal-Induced Acquired Resistance to ALK Tyrosine Kinase Inhibitors in ALK-Translocated Lung Cancer
This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway–induced acquired resistance to ALK-TKIs. To this end, ceritinib-resistant cells (H3122-CER) were established from the H3122 NSCLC cell line harboring the ALK gene rearrangement via long-term exposure to ceritinib. H3122-CER cells acquired resistance to ceritinib through EGFR bypass pathway activation. Furthermore, H3122 cells that became resistant to ceritinib or alectinib through EGFR pathway activation showed cross-resistance to other ALK-TKIs. Ceritinib and afatinib combination ...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Miyawaki, M., Yasuda, H., Tani, T., Hamamoto, J., Arai, D., Ishioka, K., Ohgino, K., Nukaga, S., Hirano, T., Kawada, I., Naoki, K., Hayashi, Y., Betsuyaku, T., Soejima, K. Tags: Signal Transduction Source Type: research
Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis
In this study, mechanistic insight was sought regarding exo-Anx II and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-Anx II in angiogenesis. Using atomic force microscopy and Western blotting, exo-Anx II expression was characterized in normal and breast cancer cells. In addition, organ-specific metastatic breast cancer cells and animal models were used to define the role exo-Anx II in breast cancer metastasis. Results revealed that exo-Anx II expression is significantly higher in malignant cells than normal and premetastatic breast can...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Maji, S., Chaudhary, P., Akopova, I., Nguyen, P. M., Hare, R. J., Gryczynski, I., Vishwanatha, J. K. Tags: Signal Transduction Source Type: research
Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells
This study indicates that ovarian cancer–derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion.
Implications: Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78–92. ©2016 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Nakamura, K., Sawada, K., Kinose, Y., Yoshimura, A., Toda, A., Nakatsuka, E., Hashimoto, K., Mabuchi, S., Morishige, K.-i., Kurachi, H., Lengyel, E., Kimura, T. Tags: Signal Transduction Source Type: research
Src Family Kinases Are Regulated in Multiple Myeloma Cells by Phosphatase of Regenerating Liver-3
In conclusion, PRL-3 protected MM cells against apoptosis by dysregulating both the total levels and the activation levels of specific SFK members that are important for IL6 signal transduction in MM cells. Eventually, this led to increased levels of Mcl-1.
Implications: This study suggests PRL-3 and SFKs are key mediators of the IL6-driven signaling events and points to both PRL-3 and SFK members as potential targets for treatment of MM. Mol Cancer Res; 15(1); 69–77. ©2016 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Abdollahi, P., Vandsemb, E. N., Hjort, M. A., Misund, K., Holien, T., Sponaas, A.-M., Ro, T. B., Slordahl, T. S., Borset, M. Tags: Signal Transduction Source Type: research
Interplay between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediates Castration Resistance
This study suggests important consequences for clinical castration resistance due to simultaneous expression of AR-FL and AR-Vs in patient tumors and suggests that dissecting these interactions should help develop effective strategies to disrupt AR-V signaling. Mol Cancer Res; 15(1); 59–68. ©2016 AACR. (Source: Molecular Cancer Research)
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Zhan, Y., Zhang, G., Wang, X., Qi, Y., Bai, S., Li, D., Ma, T., Sartor, O., Flemington, E. K., Zhang, H., Lee, P., Dong, Y. Tags: Signal Transduction Source Type: research
AXL Inhibition Suppresses the DNA Damage Response and Sensitizes Cells to PARP Inhibition in Multiple Cancers
Epithelial to mesenchymal transition (EMT) is associated with a wide range of changes in cancer cells, including stemness, chemo- and radio-resistance, and metastasis. The mechanistic role of upstream mediators of EMT has not yet been well characterized. Recently, we showed that non–small cell lung cancers (NSCLC) that have undergone EMT overexpress AXL, a receptor tyrosine kinase. AXL is also overexpressed in a subset of triple-negative breast cancers (TNBC) and head and neck squamous cell carcinomas (HNSCC), and its overexpression has been associated with more aggressive tumor behavior and linked to resistance to c...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Balaji, K., Vijayaraghavan, S., Diao, L., Tong, P., Fan, Y., Carey, J. P. W., Bui, T. N., Warner, S., Heymach, J. V., Hunt, K. K., Wang, J., Byers, L. A., Keyomarsi, K. Tags: DNA Damage and Repair Source Type: research
Exploitation of Castration-Resistant Prostate Cancer Transcription Factor Dependencies by the Novel BET Inhibitor ABBV-075
Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and hematologic malignancies. The function of BET family member BRD4 at enhancers/superenhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here, the hypothesis was tested that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the androgen receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibito...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Faivre, E. J., Wilcox, D., Lin, X., Hessler, P., Torrent, M., He, W., Uziel, T., Albert, D. H., McDaniel, K., Kati, W., Shen, Y. Tags: Chromatin, Epigenetics, and RNA Regulation Source Type: research
Autophagy Induction Results in Enhanced Anoikis Resistance in Models of Peritoneal Disease
Peritoneal carcinomatosis and peritoneal sarcomatosis is a potential complication of nearly all solid tumors and results in profoundly increased morbidity and mortality. Despite the ubiquity of peritoneal carcinomatosis/peritoneal sarcomatosis, there are no clinically relevant targeted therapies for either its treatment or prevention. To identify potential therapies, we developed in vitro models of peritoneal carcinomatosis/peritoneal sarcomatosis using tumor cell lines and patient-derived spheroids (PDS) that recapitulate anoikis resistance and spheroid proliferation across multiple cancer types. Epithelial- and mesenchym...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Chen, J. L., David, J., Cook-Spaeth, D., Casey, S., Cohen, D., Selvendiran, K., Bekaii-Saab, T., Hays, J. L. Tags: Cell Death and Survival Source Type: research
ECM Composition and Rheology Regulate Growth, Motility, and Response to Photodynamic Therapy in 3D Models of Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma is characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma associated with this disease has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how interactions with ECM, acting as a biophysical regulator of phenotype, not only a barrier to drug perfusion, regulate susceptibilities and resistance to specific therapies. In this context, an integrative approach is used to evaluate invasive b...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Cramer, G. M., Jones, D. P., El-Hamidi, H., Celli, J. P. Tags: Cell Death and Survival Source Type: research
Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes
Carcinoma-associated fibroblasts (CAF) represent a significant component of pancreatic cancer stroma and are biologically implicated in tumor progression. However, evidence of both cancer-promoting and -restraining properties amongst CAFs suggests the possibility of multiple phenotypic subtypes. Here, it is demonstrated that senescent CAFs promote pancreatic cancer invasion and metastasis compared with nonsenescent control CAFs using in vitro Transwell invasion models and in vivo xenograft mouse models. Screening by gene expression microarray and cytokine ELISA assays revealed IL8 to be upregulated in senescent CAFs. Exper...
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Authors: Wang, T., Notta, F., Navab, R., Joseph, J., Ibrahimov, E., Xu, J., Zhu, C.-Q., Borgida, A., Gallinger, S., Tsao, M.-S. Tags: Cell Cycle and Senescence Source Type: research
Highlights of This Issue
(Source: Molecular Cancer Research)
Source: Molecular Cancer Research - January 2, 2017 Category: Cancer & Oncology Tags: Highlights Source Type: research
Acknowledgment to Reviewers
(Source: Molecular Cancer Research)
Source: Molecular Cancer Research - November 30, 2016 Category: Cancer & Oncology Tags: Acknowledgment to Reviewers Source Type: research
The Cytoskeletal Adapter Protein Spinophilin Regulates Invadopodia Dynamics and Tumor Cell Invasion in Glioblastoma
Glioblastoma is a primary brain cancer that is resistant to all treatment modalities. This resistance is due, in large part, to invasive cancer cells that disperse from the main tumor site, escape surgical resection, and contribute to recurrent secondary lesions. The adhesion and signaling mechanisms that drive glioblastoma cell invasion remain enigmatic, and as a result there are no effective anti-invasive clinical therapies. Here we have characterized a novel adhesion and signaling pathway comprised of the integrin αvβ8 and its intracellular binding partner, Spinophilin (Spn), which regulates glioblastoma cell...
Source: Molecular Cancer Research - November 30, 2016 Category: Cancer & Oncology Authors: Cheerathodi, M., Avci, N. G., Guerrero, P. A., Tang, L. K., Popp, J., Morales, J. E., Chen, Z., Carnero, A., Lang, F. F., Ballif, B. A., Rivera, G. M., McCarty, J. H. Tags: Signal Transduction Source Type: research
