Cancer insights through macropinocytosis: a role for sorting nexins?

Wang, Jack T. H., Kerr, Markus and Teasdale, Rohan D. (2014). Cancer insights through macropinocytosis: a role for sorting nexins?. In The research and biology of Cancer I (pp. 1-23) Hong Kong, China: iConcept Press.

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Author Wang, Jack T. H.
Kerr, Markus
Teasdale, Rohan D.
Title of chapter Cancer insights through macropinocytosis: a role for sorting nexins?
Title of book The research and biology of Cancer I
Place of Publication Hong Kong, China
Publisher iConcept Press
Publication Year 2014
Sub-type Critical review of research, literature review, critical commentary
Open Access Status File (Publisher version)
Year available 2013
ISBN 9781922227225
Chapter number 3
Start page 1
End page 23
Total pages 23
Total chapters 16
Collection year 2015
Language eng
Formatted Abstract/Summary
Macropinocytosis is an actin-driven endocytic process, whereby membrane ruffles fold back onto the plasma membrane to form large (> 0.2 μm in diameter) endocytic organelles called macropinosomes (Swanson & Watts, 1995). The rapid and large fluid-carrying capacity of macropinosomes is central to their role in the immune response, possessing great potential for antigen sampling from the environment as the amount of material internalized greatly exceeds that of other endocytic pathways (Norbury, 2006). Studies of oncogenic signaling and cellular responses to growth factors have also implicated acropinocytosis in the molecular mechanisms of cancer and tumorigenesis. Treatment with Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF) and Hepatocyte Growth Factor/Scatter Factor (HGF/SF) - ligands associated with uncontrolled cell proliferation in cancerous tissue - have all been shown to rapidly increase the rate of macropinosome formation and fluid-phase uptake (Kerr & Teasdale,2009). Cells overexpressing oncogenes have been shown to exhibit elevated levels of macropinocytosis, as well as accelerated spontaneous motility in wound healing assays (Platek et al., 2007). This suggests a strong link between the membrane ruffling necessary for macropinosome formation and cell motility regulation, a process crucial in tumour progression and metastasis. As the molecular mechanisms of macropinocytosis become further defined a detailed evaluation of their regulation of immunological and cancerous processes is needed.

Recently, members of the Sorting Nexin (SNX) family have been localized to the dynamic ruffling cell surface and found to be associated with early-stage macropinosomes (Kerr et al., 2006; Merino-Trigo et al., 2004; J. T. Wang et al., 2010). SNX-PX-BAR proteins form a subset of the SNX family and their lipid-binding (PX) and membrane-curvature sensing (BAR) domain architecture is consistent with a potential role in the dramatic membrane remodeling and trafficking required in the initiation of macropinosome formation. Other SNX-PX-BAR proteins have also been found to interact with regulators of actin remodeling, implicating them not only in macropinocytosis but also cell motility, metastasis, and tumorigenesis. This chapter will outline the outcomes of systematic functional studies into the impact of the SNX-PX-BAR family on macropinocytosis, and the insights this will provide into the molecular mechanisms of cancer biology. 
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Created: Mon, 21 Jan 2013, 12:38:28 EST by Susan Allen on behalf of Institute for Molecular Bioscience