The RAF-MEK-ERK Pathway: Targeting ERK to Overcome Obstacles of Effective Cancer Therapy

Yu, Zutao; Ye, Shiqi; Hu, Gaoyun; Lv, Meng; Tu, Zhijun; Zhou, Kun; Li, Qianbin

doi:10.4155/fmc.14.143

Cited by 62 publications

(48 citation statements)

References 140 publications

(168 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On this basis, it has been suggested that the direct use of ERK inhibitors could overcome acquired resistance to BRAF and MEK inhibitors. Their use appears to be particularly advantageous, since mutations of ERK1/2 able to induce acquired resistance have not been described [24]. …”

Section: Erk1/2 As An Emerging Target In Anti-cancer Therapymentioning

confidence: 99%

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs

Serini

Calviello

2017

Nutrients

View full text Add to dashboard Cite

A potential complementary role of the dietary long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFA) in combination with innovative mono-targeted therapies has recently been proposed. These compounds are thought to act pleiotropically to prevent the development and progression of a variety of cancers, including breast cancer. We hereinafter critically analyze the reports investigating the ability of LCn-3 PUFA to modulate the Ras/ERK and the phosphoinositide survival signaling pathways often aberrantly activated in breast cancer and representing the main targets of innovative therapies. The in vitro or in vivo animal and human interventional studies published up to January 2017 investigating the effects of LCn-3 PUFA on these pathways in normal and cancerous breast cells or tissues were identified through a systematic search of literature in the PubMed database. We found that, in most cases, both the in vitro and in vivo studies demonstrated the ability of LCn-3 PUFA to inhibit the activation of these pro-survival pathways. Altogether, the analyzed results strongly suggest a potential role of LCn-3 PUFA as complementary agents in combination with mono-targeted therapies. Moreover, the results indicate the need for further in vitro and human interventional studies designed to unequivocally prove the potential adjuvant role of these fatty acids.

show abstract

Section: Erk1/2 As An Emerging Target In Anti-cancer Therapymentioning

confidence: 99%

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs

Serini

Calviello

2017

Nutrients

View full text Add to dashboard Cite

show abstract

“…The extracellular‐signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) pathway is a conserved signaling cascade that regulates growth, differentiation, mobility, and immunity via transmitting signals from cell surface receptors (Montagut & Settleman, ). In various tumors, such as CRC, thyroid and mammary cancer, overactivation of ERK/MAPK signaling acts as an oncogenic role and a promising target in anticancer therapeutics (Buonato & Lazzara, ; Yu et al, ). Here, we first showed BZW2 promoted the development of CRC via activating ERK/MAPK pathway, which provided a novel gene target therapy for CRC.…”

Section: Introductionmentioning

confidence: 99%

BZW2 promotes the malignant progression of colorectal cancer via activating the ERK/MAPK pathway

Huang

Chen

Fan

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most prevalent malignant solid cancers worldwide involving the dysregulation of multiple signaling molecules. However, the role and corresponding mechanism of basic leucine zipper and W2 domains 2 (BZW2) in CRC development, to our knowledge, has not been reported. We found BZW2 was overexpressed in human CRC tissues compared with that in paired adjacent colorectal samples. BZW2 overexpression was closely associated with tumor T stage (p = .030), metastatic lymph nodes (p = .037), TNM stage (p = .018) and the worse prognosis of CRC patients (p = .009). Moreover, BZW2 was an independent disadvantage prognostic factor (p = .031). BZW2 also showed an increased expression in different invasive CRC cell lines. Its silencing and overexpression diminished and increased cell proliferation, invasion, and migration in Colo205 and HCT116 cells via specifically activating of extracellular-signalregulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling. Moreover, ERK/MAPK inhibitor PD98059 reverse the enhancement of cell proliferation, invasion, and migration in BZW2 overexpressing HCT116 cells. BZW2 silencing also inhibited subcutaneous tumors growth and p-ERK expression in vivo. BZW2 promotes the malignant progression of CRC via activating ERK/MAPK signaling, which provided a promising gene target therapy for CRC. K E Y W O R D S basic leucine zipper and W2 domains 2, colorectal cancer, ERK

show abstract

“…The RAS‐RAF‐MEK‐ERK pathway is an evolutionarily conserved signaling cascade that transmits signals from cell surface receptors to promote proliferation and survival programs . Under physiological conditions, ERK signaling is tightly controlled at multiple levels by feedback loops, which are essential for regulating cell growth, and homeostasis.…”

Section: Introductionmentioning

confidence: 99%

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

Pen

Huang

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation. Furthermore, knocking out KAP1 remarkably increased the susceptibility of A549 cells to the anti-cancer drug 5-Fluorouracil, which correlated with increasing ERK phosphorylation. In vivo xenograft experiments suggested that KAP1 deficiency significantly decreases the tumorigenicity of A549 cells. Taken together, our findings indicate that KAP1 acts as a key module in the c-Raf-interactome complex and regulates lung cancer development through the Raf-MEK-ERK pathway. Therefore, KAP1 may represent a potential diagnosis biomarker and new treatment target for lung cancer.

show abstract

The RAF-MEK-ERK Pathway: Targeting ERK to Overcome Obstacles of Effective Cancer Therapy

Abstract: Taking in account the inspiring outcomes of ERK inhibitors in preclinical research, ERK1/2 might be the optimal target to overcome acquired drug resistance in RAF-MEK-ERK pathway.

Cited by 62 publications

References 140 publications

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs

BZW2 promotes the malignant progression of colorectal cancer via activating the ERK/MAPK pathway

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

Contact Info

Product

Resources

About