ArticleMolecular and cellular biology2008
Activated Kras, but not Hras or Nras, may initiate tumors of endodermal origin via stem cell expansion.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- Article
- K-Ras controls asymmetric cell divisions from the primary cilium.Cell death & disease · 2026Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Drugging Ras trafficking-are there new roads to travel?npj drug discovery · 2025Review
- Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription.Science advances · 2023Article
- K-Ras Binds Calmodulin-Related Centrin1 with Potential Implications for K-Ras Driven Cancer Cell Stemness.Cancers · 2023Article
- Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.Frontiers in genetics · 2023Article
- Targeting the undruggable oncogenic KRAS: the dawn of hope.JCI insight · 2022Review
- Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Promotion of cancer cell stemness by Ras.Biochemical Society transactions · 2021Review
- Splice variants of RAS-translational significance.Cancer metastasis reviews · 2020Review
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- IKKβ Kinase Promotes Stemness, Migration, and Invasion in KRAS-Driven Lung Adenocarcinoma Cells.International journal of molecular sciences · 2020Article
- From basic researches to new achievements in therapeutic strategies of KRAS-driven cancers.Cancer biology & medicine · 2019Article
- Article
- A model for RAS mutation patterns in cancers: finding the sweet spot.Nature reviews. Cancer · 2018Review
- RAS variant signalling.Biochemical Society transactions · 2018Review
- Status of KRAS in iPSCs Impacts upon Self-Renewal and Differentiation Propensity.Stem cell reports · 2018Article
- Article
1 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
The three closely related human Ras genes, Hras, Nras, and Kras, are all widely expressed, engage a common set of downstream effectors, and can each exhibit oncogenic activity. However, the vast majority of activating Ras mutations in human tumors involve Kras. Moreover, Kras mutations are most frequently seen in tumors of endodermally derived tissues (lung, pancreas, and colon), suggesting that activated Kras may affect an endodermal progenitor to initiate oncogenesis. Using a culture model of retinoic acid (RA)-induced stem cell differentiation to endoderm, we determined that while activated HrasV12 promotes differentiation and growth arrest in these endodermal progenitors, KrasV12 promotes their proliferation. Furthermore, KrasV12-expressing endodermal progenitors fail to differentiate upon RA treatment and continue to proliferate and maintain stem cell characteristics. NrasV12 neither promotes nor prevents differentiation. A structure-function analysis demonstrated that these distinct effects of the Ras isoforms involve their variable C-terminal domains, implicating compartmentalized signaling, and revealed a requirement for several established Ras effectors. These findings indicate that activated Ras isoforms exert profoundly different effects on endodermal progenitors and that mutant Kras may initiate tumorigenesis by expanding a susceptible stem/progenitor cell population. These results potentially explain the high frequency of Kras mutations in tumors of endodermal origin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.