Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
4.9
Journals
IJMS
Special Issues
KRAS-Associated Cancer Signaling
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

KRAS-Associated Cancer Signaling

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 629

Special Issue Editor

Dr. Sang Hun Lee

E-Mail Website
Guest Editor
Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 22332, Republic of Korea
Interests: RAS/KRAS signaling; receptor tyrosine kinases; EGFR; c-MET; PI3K–MAPK pathways; tumor microenvironment; drug resistance and adaptive rewiring; biomarker stratification; combination therapy; prion protein (PrPC)

Special Issue Information

Dear Colleagues,

Oncogenic KRAS orchestrates cancer signalling across colorectal, lung, and pancreatic malignancies through dynamic crosstalk with receptor tyrosine kinases, downstream MAPK/PI3K pathways, and the tumour microenvironment. Despite recent advances, including covalent KRASG12C inhibitors, adaptive rewiring, lineage context, and KRAS-independent survival circuits continue to limit durable responses. This Special Issue will gather mechanistic and translational studies that dissect KRAS-associated networks and therapeutic vulnerabilities, including RTK and membrane-proximal organizers (e.g., EGFR, c-MET, laminin receptor, prion protein), biomarker-driven patient stratification, and rational combinations with chemotherapy, targeted agents, or immunotherapy. We welcome original research, brief reports, and reviews using cellular and animal models, organoids, multi-omics, and computational approaches that inform clinically actionable strategies and early clinical translation.

Dr. Sang Hun Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • KRAS signaling
  • receptor tyrosine kinases
  • EGFR
  • c-MET
  • PI3K–MAPK pathways
  • tumor microenvironment
  • drug resistance and adaptive rewiring
  • combination therapy
  • biomarker stratification
  • prion protein (PrPC)

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

16 pages, 3317 KB  
Article
PrPC-Neutralizing Antibody Confers an Additive Benefit in Combination with 5-Fluorouracil in KRAS-Mutant Colorectal Cancer Models, Associated with Reduced RAS-GTP and AKT/ERK Phosphorylation
by Jeong Kun Lee, Jun Young Yoon, Jae Young Lee and Sang Hun Lee
Int. J. Mol. Sci. 2026, 27(3), 1159; https://doi.org/10.3390/ijms27031159 - 23 Jan 2026
Viewed by 447
Abstract
Colorectal cancer (CRC) remains a major cause of cancer-related deaths in advanced disease, and activating KRAS/NRAS mutations limit the use of anti-EGFR antibodies to RAS–wild-type tumors. The cellular prion protein (PrPC) has been linked to aggressive and chemoresistant CRC, but its [...] Read more.
Colorectal cancer (CRC) remains a major cause of cancer-related deaths in advanced disease, and activating KRAS/NRAS mutations limit the use of anti-EGFR antibodies to RAS–wild-type tumors. The cellular prion protein (PrPC) has been linked to aggressive and chemoresistant CRC, but its extracellular partners and functional relevance in KRAS-mutant disease are not fully defined. Here, we examined extracellular PrPC complexes and PrPC-associated signaling in CRC cell lines and xenografts using a neutralizing PrPC monoclonal antibody. Across a CRC panel that included SNU-C5/WT and its 5-fluorouracil- and oxaliplatin-resistant derivatives, HT-29 (KRAS–wild-type), and HCT-8 and LoVo (KRAS-mutant), co-immunoprecipitation showed that PrPC forms complexes with the 37/67 kDa laminin receptor (RPSA), with PrPC–RPSA association particularly increased in KRAS-mutant HCT-8 and LoVo cells. PrPC protein levels were higher in KRAS-mutant HCT-8, SW620, and SNU-407 cells than in HT-29, and PrPC neutralization reduced viability in all four lines. Accordingly, we assessed upstream RAS activity and found that active RAS (RAS-GTP) was higher in KRAS-mutant cells than in HT-29, and PrPC treatment was associated with reduced RAS-GTP levels. In the same KRAS-mutant setting, basal AKT phosphorylation exceeded that in HT-29, and PrPC treatment lowered AKT phosphorylation without changing total AKT. Moreover, PrPC treatment was associated with reduced ERK1/2 phosphorylation in KRAS-mutant cells, suggesting attenuation of downstream RAS pathway output. These signaling changes coincided with a decrease in the S-phase fraction and an increase in G1. In an HCT-8 (KRAS G13D) xenograft model, PrPC monotherapy inhibited tumor growth in a dose-dependent manner, and 5-fluorouracil (5-FU) monotherapy produced an intermediate effect. The combination of PrPC (10 mg/kg) and 5-FU (20 mg/kg) yielded the greatest tumor growth inhibition among the tested regimens. Consistent with this enhanced tumor control, immunofluorescence of xenograft tissues showed that PrPC, particularly with 5-FU, reduced intratumoral PrPC and PCNA and decreased CD31-positive microvessels and α-SMA–positive vessel structures. Taken together, these findings suggest that extracellular PrPC supports RAS–AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrPC neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The data provide a preclinical basis for evaluating PrPC antibodies in combination with fluoropyrimidine-based regimens in patients with KRAS-mutant CRC. Full article
(This article belongs to the Special Issue KRAS-Associated Cancer Signaling)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-1
Back to TopTop