Guanine nucleotide exchange factors and colon neoplasia

dc.contributor.authorNjei, Lea-Pearl
dc.contributor.authorSampaio Moura, Natalia
dc.contributor.authorSchledwitz, Alyssa
dc.contributor.authorGriffiths, Kelly
dc.contributor.authorCheng, Kunrong
dc.contributor.authorRaufman, Jean-Pierre
dc.date.accessioned2024-11-14T15:18:11Z
dc.date.available2024-11-14T15:18:11Z
dc.date.issued2024-10-17
dc.description.abstractDespite many diagnostic and therapeutic advances, colorectal cancer (CRC) remains the second leading cause of cancer death for men and women in the United States. Alarmingly, for reasons currently unknown, the demographics of this disease have shifted towards a younger population. Hence, understanding the molecular mechanisms underlying CRC initiation and progression and leveraging these findings for therapeutic purposes remains a priority. Here, we review critically the evidence that canonical and noncanonical actions of guanine nucleotide exchange factors (GEFs) play important roles in CRC evolution. Rho GEF GTPases, which switch between inactive GDP-bound and active GTP-bound states, are commonly overexpressed and activated in a variety of cancers, including CRC, and may be tractable therapeutic targets. In addition to comprehensively reviewing this field, we focus on Rho/Rac GEFs that are involved in regulating key functions of normal and neoplastic cells like cell polarity, vesicle trafficking, cell cycle regulation, and transcriptional dynamics. Prime examples of such Rho/Rac GEFs include βPak-interacting exchange factor (βPix), a Rho family GEF for Cdc42/Rac1, Tiam1, GEF-H1, RGNEF, and other GEFs implicated in CRC development and progression. Throughout this analysis, we explore how these findings fill key gaps in knowledge regarding the molecular basis of colon carcinogenesis and how they may be leveraged to treat advanced CRC. Lastly, we address potential future directions for research into the role of GEFs as CRC biomarkers and therapeutic targets. In this regard, leveraging the noncanonical actions of GEFs appears to provide a relatively unexplored opportunity requiring further investigation.
dc.description.sponsorshipThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by a Merit Review Award from the United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Program (BX004890 to JPR). Kelly Griffiths was supported by a T32 Award from the National Institutes of Health (T32 DK067872 to JPR). Lea-Pearl Njei was supported by awards from the National Institutes of Health through the National Institute of General Medical Sciences Undergraduate Research Training Initiative for Student Enhancement (U-RISE) Program at the University of Maryland, Baltimore County (UMBC) (T34GM136497) and the National Institute of Diabetes and Digestive and Kidney Diseases Short-Term Research Experience Program to Unlock Potential (STEP-UP) (1R25DK113652). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health, U.S. Department of Veterans Affairs, or the United States Government.
dc.description.urihttps://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1489321/full
dc.format.extent8 pages
dc.genrejournal articles
dc.identifierdoi:10.13016/m2zwq9-qn3u
dc.identifier.citationNjei, Lea-Pearl, Natalia Sampaio Moura, Alyssa Schledwitz, Kelly Griffiths, Kunrong Cheng, and Jean-Pierre Raufman. “Guanine Nucleotide Exchange Factors and Colon Neoplasia.” Frontiers in Cell and Developmental Biology 12 (October 18, 2024). https://doi.org/10.3389/fcell.2024.1489321.
dc.identifier.urihttps://doi.org/10.3389/fcell.2024.1489321
dc.identifier.urihttp://hdl.handle.net/11603/36889
dc.language.isoen_US
dc.publisherFrontiers
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department
dc.relation.ispartofUMBC Student Collection
dc.rightsAttribution 4.0 International CC BY 4.0 Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRho GTPases
dc.subjectGuanine Nucleotide Exchange Factors
dc.subjectcolorectal cancer
dc.subjectTiam1
dc.subjectβPak-interacting exchange factor
dc.subjectGEF-H1
dc.subjectmuscarinic receptors
dc.titleGuanine nucleotide exchange factors and colon neoplasia
dc.typeText
dcterms.creatorhttps://orcid.org/0000-0002-0787-3045

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