scholarly journals Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis

2011 ◽  
Vol 22 (3) ◽  
pp. 327-341 ◽  
Author(s):  
Nicholas O. Deakin ◽  
Christopher E. Turner
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Morphology ◽  
Molecular Mechanisms ◽  
Adhesion Formation ◽  
Three Dimensional ◽  
Rho Kinase ◽  
Adaptor Protein ◽  
Metastatic Tumor

Individual metastatic tumor cells exhibit two interconvertible modes of cell motility during tissue invasion that are classified as either mesenchymal or amoeboid. The molecular mechanisms by which invasive breast cancer cells regulate this migratory plasticity have yet to be fully elucidated. Herein we show that the focal adhesion adaptor protein, paxillin, and the closely related Hic-5 have distinct and unique roles in the regulation of breast cancer cell lung metastasis by modulating cell morphology and cell invasion through three-dimensional extracellular matrices (3D ECMs). Cells depleted of paxillin by RNA interference displayed a highly elongated mesenchymal morphology, whereas Hic-5 knockdown induced an amoeboid phenotype with both cell populations exhibiting reduced plasticity, migration persistence, and velocity through 3D ECM environments. In evaluating associated signaling pathways, we determined that Rac1 activity was increased in cells devoid of paxillin whereas Hic-5 silencing resulted in elevated RhoA activity and associated Rho kinase–induced nonmuscle myosin II activity. Hic-5 was essential for adhesion formation in 3D ECMs, and analysis of adhesion dynamics and lifetime identified paxillin as a key regulator of 3D adhesion assembly, stabilization, and disassembly.

scholarly journals Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis

2020 ◽  
pp. 72-82
Author(s):  
Mossa Gardaneh ◽  
Zahra Nayeri ◽  
Parvin Akbari ◽  
Mahsa Gardaneh ◽  
Hasan Tahermansouri
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Breast Cancer Cell Lines

Background: We investigated molecular mechanisms behind astaxanthinmediated induction of apoptosis in breast cancer cell lines toward combination therapy against cancer drug resistance. Methods: Breast cancer cell lines were treated with serial concentrations of astaxanthin to determine its IC50. We used drug-design software to predict interactions between astaxanthin and receptor tyrosine kinases or other key gene products involved in intracellular signaling pathways. Changes in gene expression were examined using RT-PCR. The effect of astaxanthin-nanocarbons combinations on cancer cells was also evaluated. Results: Astaxanthin induced cell death in all three breast cancer cell lines was examined so that its IC50 in two HER2-amplifying lines SKBR3 and BT-474 stood, respectively, at 36 and 37 ?M; however, this figure for MCF-7 was significantly lowered to 23 ?M (P<0.05). Astaxanthin-treated SKBR3 cells showed apoptotic death upon co-staining. Our in silico examinations showed that some growth-promoting molecules are strongly bound by astaxanthin via their specific amino acid residues with their binding energy standing below -6 KCa/Mol. Next, astaxanthin was combined with either graphene oxide or carboxylated multi-walled carbon nanotube, with the latter affecting SKBR cell survival more extensively than the former (P<0.05). Finally, astaxanthin coinduced tumor suppressors p53 and PTEN but downregulated the expression of growth-inducing genes in treated cells. Conclusion: These findings indicate astaxanthin carries' multitarget antitumorigenic capacities and introduce the compound as a suitable candidate for combination therapy regimens against cancer growth and drug resistance. Development of animal models to elucidate interactions between the compound and tumor microenvironment could be a major step forward towards the inclusion of astaxanthin in cancer therapy trials.

scholarly journals miR-342-5p as a Potential Regulator of HER2 Breast Cancer Cell Growth

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Evita Maria Lindholm ◽  
Suvi-Katri Leivonen ◽  
Eldri Undlien ◽  
Daniel Nebdal ◽  
Anna Git ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Breast Cancer Cell Lines ◽  
Nucleotide Exchange ◽  
Her2 Positive ◽  
Her2 Breast Cancer

Background: HER2 positive Breast Cancers (BC) have aggressive behavior and poor prognosis. Previously, we have identified miR-342-5p as an upstream regulator of HER2 signaling, as well as inhibitor of HER2 positive BC cell line growth. Objective: Here, we aimed to further investigate the molecular mechanisms behind miR-342-5pinduced HER2 pathway deregulation. </P><P> Method: Two HER2 amplified breast cancer cell lines were transiently transfected with miR-342-5p mimic or negative control, and gene expression was analyzed by Agilent microarrays. Three clinical datasets with BC patients were used to identify correlations between candidate genes and miR-342- 5p, and associations with survival. Results: Pathway analyses of all deregulated genes revealed a significant suppression of the HER2 downstream pathways ERK/MAPK and SAPK/JNK, whereas the miR-342-5p predicted target genes were enriched for pathways associated with cell motility.Biological functions linked to mitochondrial stability were ranked among the top toxicological functions in both gene lists. Among the most deregulated genes, Cytochrome B5 Reductase 3 (CYB5R3) and Rap Guanine Nucleotide Exchange Factor 6 (RAPGEF6) significantly anticorrelated and correlated, respectively, with miR-342-5p in all three clinical BC datasets. Low CYB5R3 levels and high RAPGEF6 levels were significantly associated with survival, although this was not directly associated with HER2 expression. Conclusion: Our data suggest that miR-342-5p overexpression in HER2 positive BC cell lines elicits broad effects on HER2 downstream signaling, cell motility and mitochondrial stability. Together these effects may render cells less proliferative and more sensitive to cellular stress.

Matrix stiffness and cluster size collectively regulate dormancy versus proliferation in brain metastatic breast cancer cell clusters

2020 ◽  
Vol 8 (23) ◽  
pp. 6637-6646
Author(s):  
Raghu Vamsi Kondapaneni ◽  
Shreyas S. Rao
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cell ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cluster Size ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Matrix Stiffness ◽  
Cell Clusters

Dormant versus proliferative phenotypes in metastatic tumor cell clusters are mediated via matrix stiffness and cluster size.

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