Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells-Reference-Cited by-同舟云学术

Deep top-down proteomics revealed significant proteoform-level differences between metastatic and nonmetastatic colorectal cancer cells

Published:2022-12-21 Issue:51 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

McCool Elijah N.¹^ORCID,Xu Tian¹^ORCID,Chen Wenrong²^ORCID,Beller Nicole C.³^ORCID,Nolan Scott M.¹,Hummon Amanda B.³⁴^ORCID,Liu Xiaowen⁵^ORCID,Sun Liangliang¹^ORCID

Affiliation:

1. Department of Chemistry, Michigan State University, 578 S Shaw Lane, East Lansing, MI 48824, USA.

2. Department of BioHealth Informatics, Indiana University–Purdue University Indianapolis, 719 Indiana Avenue, Indianapolis, IN 46202, USA.

3. Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA.

4. The Comprehensive Cancer Center, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA.

5. Deming Department of Medicine, School of Medicine, Tulane University, 1441 Canal Street, New Orleans, LA 70112, USA.

Abstract

Understanding cancer metastasis at the proteoform level is crucial for discovering previously unknown protein biomarkers for cancer diagnosis and drug development. We present the first top-down proteomics (TDP) study of a pair of isogenic human nonmetastatic and metastatic colorectal cancer (CRC) cell lines (SW480 and SW620). We identified 23,622 proteoforms of 2332 proteins from the two cell lines, representing nearly fivefold improvement in the number of proteoform identifications (IDs) compared to previous TDP datasets of human cancer cells. We revealed substantial differences between the SW480 and SW620 cell lines regarding proteoform and single amino acid variant (SAAV) profiles. Quantitative TDP unveiled differentially expressed proteoforms between the two cell lines, and the corresponding genes had diversified functions and were closely related to cancer. Our study represents a pivotal advance in TDP toward the characterization of human proteome in a proteoform-specific manner, which will transform basic and translational biomedical research.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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