The Ras Superfamily G-Proteins

Tetlow, Ashley L.; Tamanoi, Fuyuhiko

doi:10.1016/b978-0-12-416749-0.00001-4

Cited by 23 publications

(26 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…G proteins are composed of a G or catalytic domain, which binds guanine nucleotides and activates signaling, and a C-terminal hypervariable region (HVR) that incorporates farnesyl or prenyl groups (post-transcriptional modifications). These modifications diverge in each isoform because of the sequence variability of the HVR and locate RAS proteins to the cell membrane, where they perform their signaling function [ 38 , 39 ]. The downstream signaling is regulated by two alternative states of RAS proteins: RAS-GTP (active form) and RAS-GDP (inactive form).…”

Section: Kras Biologymentioning

confidence: 99%

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

et al. 2018

View full text Add to dashboard Cite

Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.

show abstract

Section: Kras Biologymentioning

confidence: 99%

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

et al. 2018

View full text Add to dashboard Cite

show abstract

“…This superfamily is further divided in families recognized: Ras, Rho, Arf/Sar, Ran, Rab, and Gem/Kira. 29 Mutation or overexpression of Ras superfamily G-protein has been observed in a number of human cancer cases, 30 accumulating evidence has showed that Ras oncoprotein can promote proliferation, resist apoptosis, and confer the invasive and metastatic phenotype to tumor cells. 26,29,30 Rho family GTPase is thought to be the downstream effector responsible for Ras-induced invasive and metastatic phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…29 Mutation or overexpression of Ras superfamily G-protein has been observed in a number of human cancer cases, 30 accumulating evidence has showed that Ras oncoprotein can promote proliferation, resist apoptosis, and confer the invasive and metastatic phenotype to tumor cells. 26,29,30 Rho family GTPase is thought to be the downstream effector responsible for Ras-induced invasive and metastatic phenotype. 31 RhoA regulates stress fiber formation and focal adhesion assembly that results in actomyosin contractility and contraction at the rear of the cell, which leads to translocation of the cell body.…”

Section: Discussionmentioning

confidence: 99%

Small GTPase RBJ promotes cancer progression by mobilizing MDSCs via IL-6

et al. 2016

View full text Add to dashboard Cite

RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly, but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. The forced expression of RBJ promotes tumor growth and metastasis both and. In addition, more accumulation of immune suppressive cells but less antitumor immune cell subpopulations were found in spleen and tumor tissue derived from RBJ force-expressed tumor-bearing mice. Furthermore, forced RBJ expression significantly promotes tumor cell production of pro-inflammatory cytokine IL-6 by constitutive activating MEK/ERK signaling pathway. Accordingly, RBJ knockdown significantly decreases tumor growth and metastasis and, with markedly reduced production of IL-6. Administration of anti-IL-6 neutralizing antibody could reduce MDSCs accumulation in tumor tissue . Therefore, our results demonstrate that RBJ-mediated nuclear constitutive activation of ERK1/2 leads to persistent production of IL-6 and increase of MDSCs recruitment, contributing to promotion of tumor growth and metastasis. These results suggest that RBJ contributes to tumor immune escape, maybe serving a potential target for design of antitumor drug.

show abstract

“…Each contains a catalytic domain that binds guanine nucleotides as well as a c-terminal hypervariable region (HVR) that localizes the protein to the cell membrane. 346,347 When the inactive RAS-GDP protein becomes the active form RAS-GTP, it then activates several crucial downstream pathways, including RAF/MEK/ERK and PI3K/AKT, which are necessary for cellular proliferation, apoptosis, and motility. 348,349 In NSCLC, KRAS mutations are an important oncogenic driving mutation, but therapies targeting the mutation have had limited success.…”

Section: Kras Mutationsmentioning

confidence: 99%

Targeted Therapy for Non-Small Cell Lung Cancer

Noor

Cummings

Johnson

et al. 2020

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Lung cancer is a heterogeneous disease, and the availability of comprehensive genomic profiling has allowed for the characterization of its molecular subtypes. This has increased the ability to deliver “personalized medicines” by tailoring therapies to target driver mutations in a patient's cancer. The development of targeted therapies for non-small cell lung cancer (NSCLC) has helped define the era of precision medicine throughout oncology. This article aims to contextualize recent research and provide an updated summary of targeted therapies available for patients with NSCLC. With practitioners and clinical researchers in mind, we note standard of care therapies, important approvals, practice guidelines, and treatments in development. The first section discusses mutations in the epidermal growth factor receptor (EGFR) gene, and the second section examines rearrangements in the anaplastic lymphoma kinase (ALK) and ROS1 fusions. Finally, we explore the rarer molecular alterations in BRAF, RET, MET, HER2, and KRAS. Given the many available therapies, it is important to understand the molecular alterations in NSCLC, and how to target them.

show abstract

The Ras Superfamily G-Proteins

Cited by 23 publications

References 52 publications

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

Small GTPase RBJ promotes cancer progression by mobilizing MDSCs via IL-6

Targeted Therapy for Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About