Medical Molecular Biology Commons^™

Dysregulated Gpcr Signaling And Therapeutic Options In Uveal Melanoma., Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L. Benovic, Philip B. Wedegaertner, Andrew E. Aplin

Department of Biochemistry and Molecular Biology Faculty Papers

Uveal melanoma is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage uveal melanoma. To provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated …

Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients.

METHODS: The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance.

RESULTS: The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, …

Hypoxia-Inducing Factors As Master Regulators Of Stemness Properties And Altered Metabolism Of Cancer- And Metastasis-Initiating Cells., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3'-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may …

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Recent Advances On Skin-Resident Stem/Progenitor Cell Functions In Skin Regeneration, Aging And Cancers And Novel Anti-Aging And Cancer Therapies., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging …