New insights into RAS in head and neck cancer

Jagadeeshan, Sankar; Novoplansky, Ofra Z.; Cohen, Oded; Kurth, Ina; Hess, Jochen; Rosenberg, Ari J.; Grandis, Jennifer R.; Elkabets, Moshe

doi:10.1016/j.bbcan.2023.188963

Cited by 2 publications

(3 citation statements)

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“…As NF‐κB signaling axis is a downstream pathway of ERK and PI3K/Akt and the latter two are both regulated by RAS protein, [13] it is thus hypothesized that grifolin might induce the death of A549 cells by modulating this important family of proteins. To verify this hypothesis, both immunofluorescence staining and immunoblotting assays were conducted to examine the expression of KRAS which is the most important human RAS protein related to tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

“…KRAS primarily mediates downstream signaling pathways such as RAF/MEK/ERK and PI3K/AKT/mTOR [13] . In the RAF/MEK/ERK pathway, activated KRAS‐GTP induces conformational changes of RAF, leading to the activation of the latter.…”

Section: Discussionmentioning

confidence: 99%

“…KRAS primarily mediates downstream signaling pathways such as RAF/MEK/ERK and PI3K/AKT/mTOR. [13] In the RAF/MEK/ ERK pathway, activated KRAS-GTP induces conformational changes of RAF, leading to the activation of the latter. Subsequently, RAF interacts with MEK1/2, phosphorylates and activates ERK1/2 to regulate cell proliferation, differentiation and migration.…”

Section: Discussionmentioning

confidence: 99%

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Grifolin Induces Cell Death of Human Lung Cancer A549 Cell Line via Inhibiting KRAS‐Mediated Multiple Signaling Pathways

Zhao,

Ma,

Liu

et al. 2024

Chemistry & Biodiversity

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In the current work, grifolin was obtained from the twigs and leaves of Daphne genkwa for the first time and displayed significant growth inhibition against human lung carcinoma A549 cells. Subsequent in vitro antitumor evaluation revealed that grifolin could induce remarkable cell apoptosis and G0/G1 phase arrest, as well as block cell migration and invasion. In addition, grifolin also disrupted cellular energy metabolism by inducing reactive oxygen species, reducing adenosine triphosphate and mitochondrial membrane potential, and damaging DNA synthesis. Further RNA‐seq analysis demonstrated that treatment of grifolin on A549 cells led to gene enrichment in MAPK, PI3K/Akt and NF‐kB signaling pathways, all of which were inhibited by grifolin according to immunoblotting experiments. Further mechanistical studies disclosed that the expression of a key upstream protein KRAS was also blocked, and the cell death triggered by grifolin could be rescued by a RAS activator ML‐099. Moreover, pretreatment of ML‐099 on A549 cells could reverse the grifolin‐induced downregulation of key proteins in the three aforementioned pathways. These findings indicate that grifolin could induce cell death in A549 cell line by inhibiting KRAS‐mediated multiple signaling pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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