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Full-Text Articles in Molecular Biology

Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi Jan 2018

Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase Activity And Promotes Melanoma Metastatic Behavior, Rochelle Shirin Sadeghi

Publicly Accessible Penn Dissertations

Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and MCAM, resulting in increased melanoma invasion. The mechanistic details that underlie Wnt5a-mediated regulation of APT1 activity and cellular function remains unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction of APT1 phosphorylation and we further investigate the functional role of APT1 phosphorylation on its depalmitoylating activity. We found phosphorylation increased APT1 depalmitoylating activity and reduced APT1 dimerization ...


Cell Signaling Regulatory Mechanisms Controlling Epithelial-Mesenchymal Transition In Carcinoma, Janine Marie Buonato Jan 2015

Cell Signaling Regulatory Mechanisms Controlling Epithelial-Mesenchymal Transition In Carcinoma, Janine Marie Buonato

Publicly Accessible Penn Dissertations

Epithelial-mesenchymal transition (EMT) is a cellular program normally engaged during development and wound healing that is hijacked in many cancers to drive metastasis and resistance to therapy. The clinical implications of EMT in cancer progression have driven efforts to understand the cellular processes controlling EMT induction. Transforming growth factor-beta (TGFβ) and expression of related transcription factors potentiate EMT induction through complex and incompletely understood mechanisms. In this thesis, we investigated specific intracellular signaling pathways controlling maintenance of mesenchymal characteristics and EMT induction in response to growth factors in lung and pancreatic carcinoma cells. In lung carcinoma cells, extracellular signal-regulated kinase-1 ...


Molecular Mechanisms Of Esophageal Squamous Cell Carcinoma, Apple Long Jan 2015

Molecular Mechanisms Of Esophageal Squamous Cell Carcinoma, Apple Long

Publicly Accessible Penn Dissertations

MOLECULAR MECHANISMS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Apple Long

Anil K. Rustgi

Esophageal squamous cell cancer (ESCC) is the 6th leading cause of cancer related deaths amongst American men. Although rare, this disease has a high mortality rate with a 5-year survival of 17%. Incidentally TP53 mutation is the most common genetic alteration in ESCC, along with over expression of EGFR and CYCLIN D1. We have previously modeled the invasive features of ESCC, through an in vivo-like 3D organotypic culture system, utilizing primary epithelial cells that have been transformed by overexpression of mutant TP53 and EGFR. From this model, a ...