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Jan 04, 2019

RPG Seminar Series (Speaker: Miss CHAN Chui Kuen/Miss ZHU Yun)

Date: Friday, 4 January 2019

Venue: Seminar Room 5, LG1/F
Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Time: 5:00 p.m.

Title: Site-Directed MT1-MMP Surface Insertion Regulates Neuromuscular Synaptogenesis via Focal ECM Degradation
Speaker: Miss CHAN Chui Kuen (PhD candidate)

At vertebrate neuromuscular junctions (NMJs), the basal lamina in the synaptic cleft consists of different extracellular matrix (ECM) proteins that induce and maintain synaptic specializations. Local modulation of ECM environment is believed to affect the synaptic structure and plasticity. Here, we first report that ECM-induced podosome-like structures (PLSs) cause ECM degradation focally at perforated acetylcholine receptor (AChR) clusters in Xenopus muscle cultures. Mechanistically, the intracellular trafficking and surface insertion of membrane-type 1-matrix metalloproteinase (MT1-MMP) are targeted to AChR clusters at both the core and cortex domains of PLSs through microtubule-capturing mechanisms, which in turn control the assembly and stability of AChR clusters. Upon synaptic induction, we further identify a bi-functional role of MT1-MMP in regulating nerve-induced AChR cluster formation and aneural cluster dispersal. Collectively, this study reveals that PLS-directed surface insertion of MT1-MMP modulates the local ECM environment for promoting the formation and topological remodeling of postsynaptic specializations at developing NMJs.

Title: Role and mechanism of serglycin in promoting esophageal cancer invasion and metastasis
Speaker: Miss ZHU Yun (PhD candidate)

Esophageal cancer ranks sixth in mortality rate among cancer diseases. A better understanding of the molecular mechanisms underlying esophageal cancer progression is needed to identify novel diagnostic markers and therapeutic targets. Our previous study showed that serglycin (SRGN), a proteoglycan with a core protein containing an attachment region for glycosaminoglycan (GAG) side chains, is the top upregulated gene in a highly invasive esophageal squamous cell carcinoma (ESCC) cell subline. Its significance in esophageal cancer is not well understood. The current study investigates the functional role of SRGN in ESCC. We found that SRGN promotes ESCC cell migration and invasion in vitro through regulation of phosphorylated extracellular signal-regulated kinase (p-ERK) level. We also found that the conditioned medium (CM) from SRGN-overexpressing ESCC cells stimulated the invasion ability of less invasive ESCC cells by upregulating midkine (MDK), and that this autocrine effect relies on integrity of the GAG attachment domain of SRGN.