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A proteomic investigation to discover candidate proteins involved in novel mechanisms of 5-fluorouracil resistance in colorectal cancer
Duran, M. Ortega Shaheed, Sadr-ul Sutton, Chris W.
Duran, M. Ortega
Shaheed, Sadr-ul
Sutton, Chris W.
Publication Date
2024-02
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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openAccess
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2024-02-10
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Abstract
One of the main obstacles to therapeutic success in colorectal cancer (CRC) is the development
of acquired resistance to treatment with drugs such as 5-fluorouracil (5-FU). Whilst some
resistance mechanisms are well known, it is clear from the stasis in therapy success rate that much is
still unknown. Here, a proteomics approach is taken towards identification of candidate proteins
using 5-FU-resistant sublines of human CRC cell lines generated in house. Using a multiplexed stable
isotope labelling with amino acids in cell culture (SILAC) strategy, 5-FU-resistant and equivalently
passaged sensitive cell lines were compared to parent cell lines by growing in Heavy medium with
2D liquid chromatography and Orbitrap Fusion™ Tribrid™ Mass Spectrometry analysis. Among
3003 commonly quantified proteins, six (CD44, APP, NAGLU, CORO7, AGR2, PLSCR1) were found
up-regulated, and six (VPS45, RBMS2, RIOK1, RAP1GDS1, POLR3D, CD55) down-regulated. A total
of 11 of the 12 proteins have a known association with drug resistance mechanisms or role in CRC
oncogenesis. Validation through immunodetection techniques confirmed high expression of CD44
and CD63, two known drug resistance mediators with elevated proteomics expression results. The
information revealed by the sensitivity of this method warrants it as an important tool for elaborating
the complexity of acquired drug resistance in CRC.
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Citation
Duran MO, Shaheed S, Sutton CW et al (2024) A proteomic investigation to discover candidate proteins involved in novel mechanisms of 5-fluorouracil resistance in colorectal cancer. Cells. 13(4): 342.
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