• Home
  • Search Results
  • Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses.

Concurrent depletion of Vps37 proteins evokes ESCRT-I destabilization and profound cellular stress responses.

Journal of cell science (2021-01-10)
Krzysztof Kolmus, Purevsuren Erdenebat, Ewelina Szymańska, Blair Stewig, Krzysztof Goryca, Edyta Derezińska-Wołek, Anna Szumera-Ciećkiewicz, Marta Brewińska-Olchowik, Katarzyna Piwocka, Monika Prochorec-Sobieszek, Michał Mikula, Marta Miączyńska

Molecular details of how endocytosis contributes to oncogenesis remain elusive. Our in silico analysis of colorectal cancer (CRC) patients revealed stage-dependent alterations in the expression of 112 endocytosis-related genes. Among them, transcription of the endosomal sorting complex required for transport (ESCRT)-I component VPS37B was decreased in the advanced stages of CRC. Expression of other ESCRT-I core subunits remained unchanged in the investigated dataset. We analyzed an independent cohort of CRC patients, which also showed reduced VPS37A mRNA and protein abundance. Transcriptomic profiling of CRC cells revealed non-redundant functions of Vps37 proteins. Knockdown of VPS37A and VPS37B triggered p21 (CDKN1A)-mediated inhibition of cell proliferation and sterile inflammatory response driven by the nuclear factor (NF)-κB transcription factor and associated with mitogen-activated protein kinase signaling. Co-silencing of VPS37C further potentiated activation of these independently induced processes. The type and magnitude of transcriptional alterations correlated with the differential ESCRT-I stability upon individual and concurrent Vps37 depletion. Our study provides novel insights into cancer cell biology by describing cellular stress responses that are associated with ESCRT-I destabilization.

Product Number
Product Description

Cell Proliferation ELISA, BrdU (colorimetric), sufficient for ≤1,000 tests
Triton X-100, laboratory grade
M-MLV Reverse Transcriptase, Moloney Murine Leukemia Virus enzyme & buffer for cDNA synthesis
Random Nonamers, for use as primers in cDNA synthesis, 50 μM in H2O
Minimum Essential Medium Eagle, With Earle′s salts and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
L-Glutamine solution, 200 mM, solution, sterile-filtered, BioXtra, suitable for cell culture
Phosphatase Inhibitor Cocktail 2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Oligo(dT)23, Anchored, 70 μM in H2O
Phosphatase Inhibitor Cocktail 3, DMSO solution
Trypsin-EDTA solution, 0.25%, sterile-filtered, BioReagent, suitable for cell culture, 2.5 g porcine trypsin and 0.2 g EDTA • 4Na per liter of Hanks′ Balanced Salt Solution with phenol red