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Proceedings Paper

Quantitative fluorescence nanoscopy for cancer biomedicine
Author(s): Tao Huang; Andrew Nickerson; Alec Peters; Xiaolin Nan
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Paper Abstract

Cancer is a major health threat worldwide. Options for targeted cancer therapy, however, are often limited, in a large part due to our incomplete understanding of how key processes including oncogenesis and drug response are mediated at the molecular level. New imaging techniques for visualizing biomolecules and their interactions at the nanometer and single molecule scales, collectively named fluorescence nanoscopy, hold the promise to transform biomedical research by providing direct mechanistic insight into cellular processes. We discuss the principles of quantitative single-molecule localization microscopy (SMLM), a subset of fluorescence nanoscopy, and their applications to cancer biomedicine. In particular, we will examine oncogenesis and drug resistance mediated by mutant Ras, which is associated with ~1/3 of all human cancers but has remained an intractable drug target. At ~20 nm spatial and single-molecule stoichiometric resolutions, SMLM clearly showed that mutant Ras must form dimers to activate its effector pathways and drive oncogenesis. SMLM further showed that the Raf kinase, one of the most important effectors of Ras, also forms dimers upon activation by Ras. Moreover, treatment of cells expressing wild type Raf with Raf inhibitors induces Raf dimer formation in a manner dependent on Ras dimerization. Together, these data suggest that Ras dimers mediate oncogenesis and drug resistance in tumors with hyperactive Ras and can potentially be targeted for cancer therapy. We also discuss recent advances in SMLM that enable simultaneous imaging of multiple biomolecules and their interactions at the nanoscale. Our work demonstrates the power of quantitative SMLM in cancer biomedicine.

Paper Details

Date Published: 21 August 2015
PDF: 6 pages
Proc. SPIE 9550, Biosensing and Nanomedicine VIII, 95500O (21 August 2015); doi: 10.1117/12.2188279
Show Author Affiliations
Tao Huang, Oregon Health and Science Univ. (United States)
Andrew Nickerson, Oregon Health and Science Univ. (United States)
Alec Peters, Oregon Health and Science Univ. (United States)
Xiaolin Nan, Oregon Health and Science Univ. (United States)

Published in SPIE Proceedings Vol. 9550:
Biosensing and Nanomedicine VIII
Hooman Mohseni; Massoud H. Agahi; Manijeh Razeghi, Editor(s)

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