+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer

, : CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer. Breast Cancer Research and Treatment 152(2): 337-346

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with generally poor prognosis and no available targeted therapies, highlighting a critical unmet need to identify and characterize novel therapeutic targets. We previously demonstrated that CIB1 is necessary for cancer cell survival and proliferation via regulation of two oncogenic signaling pathways, RAF-MEK-ERK and PI3K-AKT. Because these pathways are often upregulated in TNBC, we hypothesized that CIB1 may play a broader role in TNBC cell survival and tumor growth. Methods utilized include inducible RNAi depletion of CIB1 in vitro and in vivo, immunoblotting, clonogenic assay, flow cytometry, RNA-sequencing, bioinformatics analysis, and Kaplan-Meier survival analysis. CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested. Analysis of components related to PI3K-AKT and RAF-MEK-ERK signaling revealed that elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion. Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo. RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death. CIB1 expression levels per se did not predict TNBC susceptibility to CIB1 depletion, and CIB1 mRNA expression levels did not associate with TNBC patient survival. Our data are consistent with the emerging concept of non-oncogene addiction, where a large subset of TNBCs depend on CIB1 for cell survival and tumor growth, independent of CIB1 expression levels. Our data establish CIB1 as a novel therapeutic target for TNBC.


PMID: 26105795

DOI: 10.1007/s10549-015-3458-4

Other references

Boyce, T.G.; Craig, A.S.; Schaffner, W.; Dermody, T.S., 1998: Fever and encephalopathy in two school age boys. The case reports of 2 boys from Tennessee, USA, are reported. The first boy was 10 years old and reported severe headaches accompanied by vomiting, and a raised temperature. The 1st boy suffered 2 focal seizures of the right temporal region, which...

Ellis, J.M.; Shaw, D.R.; Barrentine, W.L., 1998: Soybean (Glycine max) seed quality and harvesting efficiency as affected by low weed densities. Field experiments were conducted near Brooksville, Mississippi, in 1995 and 1996 to determine the density of five weeds necessary to warrant desiccation treatment in soyabeans cv. NK 4260. There were no consistent differences in losses of harvesta...

O'donoghue, D.P.; Hyland, J.M.; O'grady, H.; Grant, D.; Sheahan, K., 1999: Colorectal cancer and ulcerative colitis - A reappraisal of surveillance colonoscopy. Gastroenterology 116(4 PART 2): A477, April

Gordon, A.R.; Siegman, M.J., 1971: Mechanical properties of smooth muscle. II. Active state. American Journal of Physiology 221(5): 1250-1254

Xia, X-Dong.; Lu, L-Qiu.; Liu, W-Qiang.; Chen, D-Zhen.; Zheng, Y-Han.; Wu, L-Zhu.; Xiao, W-Jing., 2016: Visible-Light-Driven Photocatalytic Activation of Inert Sulfur Ylides for 3-Acyl Oxindole Synthesis. Bicarbonyl-substituted sulfur ylide is a useful, but inert reagent in organic synthesis. Usually, harsh reaction conditions are required for its transformation. For the first time, it was demonstrated that a new, visible-light photoredox catalytic...

Caterini, H.R.; Rubinos, M.; Kaminetzky, H.A., 1972: Amniography during subsequent pregnancy for evaluating the post-cesarean section uterine scar. Obstetrics and Gynecology 39(5): 717-720

Wang, D.; Liu, Y.; Jiang, T.; Zhang, G.; Yuan, G.; He, J.; Su, C.; Yang, N., 2016: Seroprevalence and genotypes of Toxoplasma gondii isolated from pigs intended for human consumption in Liaoning province, northeastern China. Genetic information for Toxoplasma gondii isolates from pigs in eastern, south, and southwestern regions of China has been reported previously. However, there are no data from pigs in the northeastern area of the country. To better understand the...

Mari, E.; Maririzzatti, E., 1964: Latest Observations On The Subject Of Carbon Monoxide Poisoning And General Adaptation Syndrome. Minerva Medicolegale; Archivio di Antropologia Criminale, Psichiatria, E Medicina Legale 84: 162-167

Bii, S.C.; Otieno-Nyunya, B.; Siika, A.; Rotich, J.K., 2008: Infant feeding practices among HIV infected women receiving prevention of mother-to-child transmission services at Kitale District Hospital, Kenya. To determine the types and modes of infant feeding practices among the HIV infected mothers on prevention of mother-to-child transmission (PMTCT) and attending MCH-FP clinic at Kitale District Hospital, Kenya. Descriptive cross-sectional study. Ki...

Arko, F.R.; Lee, E.; Zarins, C.K.; Fogarty, T.J., 2004: Controlled localized thrombolysis with the "turbo" trellis to treat acute arterial occlusions following major surgery. To present the management of acute arterial ischemia following major abdominal and orthopedic surgery using a percutaneous thrombectomy device and a low dose of thrombolytic agent. A 38-year-old woman with T-8 paraplegia from a traumatic fall deve...