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Keratin-associated Proteins in Basal Cells of Tumorigenic and Highly Malignant Airway Epithelia

Olatona, Olusola Andrew
http://orcid.org/0009-0001-3049-2849
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688759563316062

Abstract Details

2023, Master of Science (MS), Bowling Green State University, Biological Sciences.
All epithelia are characterized by keratins, which make up a type of intermediate filament (IF). In epithelial tumors, which account for the majority of clinical cancers, the loss of cytoskeletal integration is considered one of the first alterations in epithelial metaplasia. This may have something to do with the expression of keratins or rearrangement of keratin filaments. In this study, I employed shotgun proteomic analysis and bioinformatic tools to identify proteins that interact with keratin filaments and thus may contribute to the disintegration of cytoskeleton. Using four airway epithelial cell lines in culture, I confirmed they highly expressed Keratin 14 (K14) and its obligatory partners, Keratin 5 (K5) or Keratin 6A (K6A). This suggests that the predominant IF is made up of K14 paired with K5/K6A. Although samples were enriched in keratin-associated proteins by immunoprecipitation (IP) with an antibody directed against K14 and K17, additional keratins not specifically targeted were also captured. Proteomic analysis revealed a list of non-keratin proteins enriched by IP. Some were associated with actin and microtubules, 23 and 6 proteins, respectively. Most of these were not linearly related to keratin content by abundance, but the motor protein, dynein I heavy chain, showed a Pearson correlation coefficient (CC) of -0.84 with keratin. Similarly, of 54 proteins associated with focal adhesions, intercellular junctions, or membranes, only septin-9 had a CC suggesting its abundance tracked with that of keratins. Finally, I analyzed IP-specific proteins that were cytosolic or had unknown subcellular distribution. A CC of -0.91 was found for one of these proteins, namely 26S proteasome regulatory subunit 8 (Psmc5). Further investigation and validation of the dataset was done by GO Enrichment Analysis. Using a subset of proteins highly concentrated by IP, compared to controls, I found the GO functions predicted were intracellular transport, translation initiation, epithelial cell migration, and filopodium assembly. This result suggests that the method may have value for unraveling the functions of the proteins and the pathways in which they operate. Integration of proteomic analysis and bioinformatic approaches may have promise for unraveling the molecular mechanisms underlying disintegration of cytoskeletal integrity in highly malignant cells.
Carol Heckman, Ph.D (Committee Chair)
Michael Geusz, Ph.D (Committee Member)
Xiaohong Tan, Ph.D (Committee Member)
194 p.
Bioinformatics; Biology; Biomedical Research; Cellular Biology; Molecular Biology; Oncology
Biological Sciences; Cell Biology; Cancer Biology; Keratins in Epithelia Tumors; Keratin; Cytokeratin; Keratin IF; Intermediate filament; IF; Cytoskeleton; Airway Epithelia; Airway Epithelial Lines; Interactomics; Mass Spectrometry; LS/MS/MS; Liquid Chromatography; Malignancy; Immunoprecipitation; IP; Proteomics; Gene Ontology;

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Citations

  • Olatona, O. A. (2023). Keratin-associated Proteins in Basal Cells of Tumorigenic and Highly Malignant Airway Epithelia [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688759563316062

    APA Style (7th edition)

  • Olatona, Olusola. Keratin-associated Proteins in Basal Cells of Tumorigenic and Highly Malignant Airway Epithelia. 2023. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688759563316062.

    MLA Style (8th edition)

  • Olatona, Olusola. "Keratin-associated Proteins in Basal Cells of Tumorigenic and Highly Malignant Airway Epithelia." Master's thesis, Bowling Green State University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688759563316062

    Chicago Manual of Style (17th edition)

bgsu1688759563316062
113
© 2023, all rights reserved.
This open access ETD is published by Bowling Green State University and OhioLINK.