Lipid remodeling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining membrane homeostasis

Abstract

Membranes are crucial cell components underlying optimal cellular functioning under diverse conditions including cancer. The membrane physiology requires acute maintenance of biophysical properties and a regulation of cellular lipidome. Homeostatic adaptation of membranes to temperature, pressure and anti-cancer drugs is a well-recognized. However, how the same is regulated under the influence of oxygen deprivation in pancreatic cancers-highly hypoxic cancer- is not known. Here, we report robust lipidomic remodelling in response to HIF-1α induction in pancreatic cancer cells and significant accumulation of lipid droplets. The lipidome rewiring span changes across various lipid classes, levels of unsaturation and acyl chain lengths. Interestingly, despite extensive lipidome alteration, cellular membrane homeostatic response ensures no major modulation of membrane biophysical properties underlying enhanced migratory potential. The correlation of lipidome changes, with pathway analysis and proteomics provide the basis for mutually exclusive regulation of lipidome and membrane properties. These findings help to understand the hypoxic regulation of pancreatic membrane homeostasis.

Single-Cell Untargeted Lipidomics Using Liquid Chromatography and Data-Dependent Acquisition after Live Cell Selection

“…Figure A shows the lipid coverage for 11 individually analyzed PANC-1 single-cells with 160 ± 8 lipids. This is similar to previously reported measurements of bulk PANC-1 cells. ,, …”

“…This is similar to previously reported measurements of bulk PANC-1 cells. 22,27,28 Referring to Table 1, the limit of detection for PC (33:1-d7) was 3.55 fmol. Calculating the theoretical concentration of PC (34:1) in a single cell based on an average from PANC-1 cells at 28 cells/μL (119 pmol/mL; n = 5) results in a theoretical concentration of 4.24 fmol of PC (34:1) in one cell.…”

Identification and benchmarking of Myokinasib-II as a highly selective and potent chemical probe for exploring MLCK1 inhibition

“…in contact mode. [49] In brief, NIH3T3 cells were seeded on 60 mm petri dish and after the attachment cells were treated with 10 µM of Myokinasib-II, 6I, Myokinasib, ML-7 and Y27632. To acquire force spectra, cantilevers (Silicon nitride) were indented at the periphery of the cell, with a spring constant of 37.55 pN/nm.…”