Figure 1 from Acquisition of Resistance to RAS Inhibition Is Associated with the Upregulation of Macropinocytosis through Both PI3K-Dependent and -Independent Signaling

作者：Ryan N. Robb, Sarah E. Ackermann, Seamus E. Degan, Khalilah E. Taylor, Runying Y. Yang, Alexander Zuniga. Marler, Valerie S. Calvert, Mariaelena Pierobon, Scott P. Lyons, Natalie K. Barker, Aurora Cabrera, Antje Schaefer, Laura E. Herring, Adrienne D. Cox, Emanuel F. Petricoin, Clint A. Stalnecker, Kirsten L. Bryant · 年份：2026 · DOI：10.1158/2767-9764.33102988 · 研究领域：Chemistry、Molecular biology、Cell biology、Cancer research、Biology

Downregulation of macropinocytosis is not sustained following genetic loss of KRAS in KRAS-mutant PDAC cell lines. A, Representative images of macropinosomes labeled with FITC–dextran (green) and nuclear DAPI stain (blue) in indicated KRAS-mutant PDAC cells transiently transfected with an siRNA oligonucleotide (10 nmol/L) against KRAS (siKRAS) or a nonspecific control (siNS) for indicated time points. Images are representative of 10 fields of view analyzed in each of three independent experiments. Scale bars, 20 μm. B, Quantification of (A), in which the total area of macropinosomes (FITC–dextran immunofluorescence) was calculated and normalized to cell number [macropinocytic (MP) index]. The relative MP index is plotted, with each individual data point representing one field containing at least 10 analyzed cells. Data for MIA PaCa-2, Pa14C, and Pa16C are presented as the mean ± SD of one experiment that is representative of three independent experiments. *, ρ < 0.05 and ****, ρ < 0.0001, by the unpaired Student t test, comparing against NS. C, Immunoblots of indicated KRAS-mutant PDAC cell lines treated with siNS and siKRAS as in A. Vinculin levels were used to monitor equivalent total protein loading. Blots are representative of three independent experiments. D, Macropinocytosis was measured via flow cytometry in KRAS-mutant PDAC cell lines that were treated with siRNA oligonucleotides as in A. Macropinocytosis was quantified via TMR–dextran labeling. Data are presented as ...