@article {731, title = {Tumor mechanics and metabolic dysfunction.}, journal = {Free Radic Biol Med}, volume = {79}, year = {2015}, month = {2015 Feb}, pages = {269-80}, abstract = {

Desmosplasia is a characteristic of most solid tumors and leads to fibrosis through abnormal extracellular matrix (ECM) deposition, remodeling, and posttranslational modifications. The resulting stiff tumor stroma not only compromises vascular integrity to induce hypoxia and impede drug delivery, but also promotes aggressiveness by potentiating the activity of key growth, invasion, and survival pathways. Intriguingly, many of the protumorigenic signaling pathways that are mechanically activated by ECM stiffness also promote glucose uptake and aerobic glycolysis, and an altered metabolism is a recognized hallmark of cancer. Indeed, emerging evidence suggests that metabolic alterations and an abnormal ECM may cooperatively drive cancer cell aggression and treatment resistance. Accordingly, improved methods to monitor tissue mechanics and metabolism promise to improve diagnostics and treatments to ameliorate ECM stiffening and elevated mechanosignaling may improve patient outcome. Here we discuss the interplay between ECM mechanics and metabolism in tumor biology and suggest that monitoring these processes and targeting their regulatory pathways may improve diagnostics, therapy, and the prevention of malignant transformation.

}, issn = {1873-4596}, doi = {10.1016/j.freeradbiomed.2014.11.020}, author = {Tung, Jason C and Barnes, J Matthew and Desai, Shraddha R and Sistrunk, Christopher and Conklin, Matthew W and Schedin, Pepper and Eliceiri, Kevin W and Keely, Patricia J and Seewaldt, Victoria L and Weaver, Valerie M} } @article {381, title = {CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.}, journal = {Cancer Epidemiol Biomarkers Prev}, volume = {18}, year = {2009}, month = {2009 Mar}, pages = {901-14}, abstract = {

BACKGROUND: Only 5\% of all breast cancers are the result of BRCA1/2 mutations. Methylation silencing of tumor suppressor genes is well described in sporadic breast cancer; however, its role in familial breast cancer is not known.

METHODS: CpG island promoter methylation was tested in the initial random periareolar fine-needle aspiration sample from 109 asymptomatic women at high risk for breast cancer. Promoter methylation targets included RARB (M3 and M4), ESR1, INK4a/ARF, BRCA1, PRA, PRB, RASSF1A, HIN-1, and CRBP1.

RESULTS: Although the overall frequency of CpG island promoter methylation events increased with age (P\<0.0001), no specific methylation event was associated with age. In contrast, CpG island methylation of RARB M4 (P=0.051), INK4a/ARF (P=0.042), HIN-1 (P=0.044), and PRA (P=0.032), as well as the overall frequency of methylation events (P=0.004), was associated with abnormal Masood cytology. The association between promoter methylation and familial breast cancer was tested in 40 unaffected premenopausal women in our cohort who underwent BRCA1/2 mutation testing. Women with BRCA1/2 mutations had a low frequency of CpG island promoter methylation (15 of 15 women had

CONCLUSIONS: This is the first evidence of CpG island methylation of tumor suppressor gene promoters in non-BRCA1/2 familial breast cancer.

}, keywords = {Biopsy, Fine-Needle, Breast Neoplasms, Chi-Square Distribution, CpG Islands, Cyclin-Dependent Kinase Inhibitor p16, Cytokines, DNA Methylation, Female, Genes, BRCA1, Genes, BRCA2, Genes, Tumor Suppressor, Humans, Mutation, Polymerase Chain Reaction, Premenopause, Promoter Regions, Genetic, Receptors, Progesterone, Receptors, Retinoic Acid, Risk, Risk Assessment, Statistics, Nonparametric, Tumor Suppressor Proteins}, issn = {1055-9965}, doi = {10.1158/1055-9965.EPI-08-0875}, author = {Vasilatos, Shauna N and Broadwater, Gloria and Barry, William T and Baker, Joseph C and Lem, Siya and Dietze, Eric C and Bean, Gregory R and Bryson, Andrew D and Pilie, Patrick G and Goldenberg, Vanessa and Skaar, David and Paisie, Carolyn and Torres-Hernandez, Alejandro and Grant, Tracey L and Wilke, Lee G and Ibarra-Drendall, Catherine and Ostrander, Julie H and D{\textquoteright}Amato, Nicholas C and Zalles, Carola and Jirtle, Randy and Weaver, Valerie M and Seewaldt, Victoria L} }