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Full-Text Articles in Medicine and Health Sciences

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner Aug 2017

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAFV600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAFV600E/ERK signaling and Abl kinases. We demonstrate that BRAFV600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …


Paracrine Regulation Of Melanocyte Genomic Stability: A Focus On Nucleotide Excision Repair, Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio May 2017

Paracrine Regulation Of Melanocyte Genomic Stability: A Focus On Nucleotide Excision Repair, Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio

Markey Cancer Center Faculty Publications

UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multistep process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage‐containing strand 3′ and 5′ to the photolesion, synthesis of a sequence‐appropriate replacement strand, and finally ligation to restore continuity of genomic …


The Soy-Derived Peptide Lunasin Inhibits Invasive Potential Of Melanoma Initiating Cells, Chris Shidal, Jun-Ichi Inaba, Kavitha Yaddanapudi, Keith R. Davis Mar 2017

The Soy-Derived Peptide Lunasin Inhibits Invasive Potential Of Melanoma Initiating Cells, Chris Shidal, Jun-Ichi Inaba, Kavitha Yaddanapudi, Keith R. Davis

Plant Pathology Faculty Publications

Lunasin is a 44 amino acid peptide with multiple functional domains including an aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We recently showed that Lunasin induced a phenotype switch of cancer initiating cells (CIC) out of the stem compartment by inducing melanocyte-associated differentiation markers while simultaneously reducing stem-cell-associated transcription factors. In the present study, we advance the hypothesis that Lunasin can reduce pools of melanoma cells with stem cell-like properties, and demonstrate that Lunasin treatment effectively inhibits the invasive potential of CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice …