Article
Biochemistry & Molecular Biology
Byeong Hyeok Choi, Ziyue Kou, Tania Marlyn Colon, Chih-Hong Chen, Yuan Chen, Wei Dai
Summary: Radil, a downstream effector of Ras, interacts strongly with KRas and GTP-bound Ras, suggesting a role in Ras activation. Overexpression of Radil leads to transient activation of MAPK signaling, while Radil knockdown weakens downstream Ras signaling, affecting cell proliferation, invasion, and migration. Radil plays a vital role in regulating Ras signaling, cell adhesion, and the epithelial-mesenchymal transition, potentially offering new opportunities for Ras-related anticancer drug development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Kelsie J. Anson, Giulia A. Corbet, Amy E. Palmer
Summary: In this study, the researchers investigated how changes in intracellular zinc ion levels affect kinase signaling pathways using fluorescent biosensors and cell perturbations. The results showed that zinc ion fluctuations are not toxic and do not activate stress-dependent kinase signaling. Additionally, the study demonstrated that while zinc ions can inhibit phosphatases, ERK and Akt are primarily activated through upstream signaling pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Genetics & Heredity
Ana Herrero, Piero Crespo
Summary: Signals transmitted through the RAS-ERK pathway play a crucial role in cancer-related cellular processes. RAS dimerization, especially at membrane microdomains, is essential for RAF activation and can be targeted pharmacologically to prevent tumorigenesis.
Article
Multidisciplinary Sciences
Lick Pui Lai, Nicole Fer, William Burgan, Vanessa E. Wall, Bingfang Xu, Daniel Soppet, Dominic Esposito, Dwight Nissley, Frank McCormick
Summary: RAF inhibitors unexpectedly activate ERK signaling in both normal and tumor cells with elevated RAS activity. This study demonstrates that RAF inhibitors can cause paradoxical ERK activation in KRAS(G12C)-dependent lung cancer cell lines. It also reveals that classical RAS proteins are not essential for this process, and the MRAS/SHOC2 complex plays a vital role.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Miguel A. Zaballos, Adrian Acuna-Ruiz, Marta Morante, Garcilaso Riesco-Eizaguirre, Piero Crespo, Pilar Santisteban
Summary: The study demonstrates that BRAF- and RAS-mutant thyroid cells respond differently to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 exhibits significant anti-tumor effects against BRAF-mutant cells in vivo, while the anti-tumor effects are mild for RAS-mutant cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jianjiang Hu, Xiaowei Gong, Staffan Stromblad
Summary: Cells probe their microenvironment using membrane protrusion-retraction cycles. Spatial and temporal coordination between Rac1 and RhoA GTP-binding activities play critical roles in initiating and reinforcing protrusions and retractions. Rac1-GTP levels increase before protrusions, while RhoA-GTP levels increase before retractions. Rac1-GTP nadirs and peaks coincide with maximal edge velocity of local membrane protrusions and retractions, followed by declined edge velocity. The alteration of local Rac1-GTP precedes the alteration of traction force. Through optogenetic Rac1-GTP perturbations, we demonstrate the fundamental role of Rac1 in restricting the size and durability of protrusions and retractions, possibly through controlling traction forces.
Article
Cell Biology
Zigen Lin, Xiaozhu Tang, Yuhao Cao, Lijin Yang, Mingmei Jiang, Xinying Li, Jie Min, Bing Chen, Ye Yang, Chunyan Gu
Summary: CD229 plays an oncogenic role in multiple myeloma by promoting cell proliferation through regulating the RAS/ERK signaling pathway.
Article
Neurosciences
Yi-Heng Pan, Jing Chen, Cui Sun, Ji-Fen Ma, Xia Li
Summary: The study revealed that Ras-GRF1 was upregulated in glioma tissues and correlated with the malignancy and prognosis of the tumors. Silencing Ras-GRF1, through mediating the H-Ras/ERK pathway, could suppress the growth and metastasis of glioma.
Review
Biochemistry & Molecular Biology
Marta Morante, Atanasio Pandiella, Piero Crespo, Ana Herrero
Summary: Metastatic melanoma is an immunogenic tumor with poor survival rates, being targeted by immune checkpoint inhibitors. Despite improvements in overall survival rates, melanoma cells develop resistance mechanisms. The combination of RAS-ERK pathway inhibitors and ICI therapy shows promising advantages for treatment.
Article
Biochemistry & Molecular Biology
Meiling Wang, Jie Liu, Yizeng Tu, Zihan Zhao, Jingjing Qu, Ka Chen, Yonglong Chen, Ying Sun, Hui Zhao, Yi Deng, Chuanyue Wu
Summary: Our study reveals that the focal adhesion protein RSU1 plays a critical role in suppressing ERK signaling during cell-ECM detachment through its interaction with prohibitin 2 (PHB2) in lipid rafts. The binding between RSU1 and PHB2 at specific sites is essential for the activation of ERK signaling in response to ECM adhesion. When cells detach from ECM, RSU1 associates with lipid rafts and interacts with PHB2, ultimately leading to downregulation of ERK signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Carsten Baltes, Divyendu Goud Thalla, Uli Kazmaier, Franziska Lautenschlaeger
Summary: Actin plays a crucial role in maintaining cell shape and generating forces. By stabilizing actin filaments with miuraenamide A, we observed a decrease in filament dynamics and an elongation of filament length, resulting in altered cell migration speed and nuclear position.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Reiko Sugiura, Ryosuke Satoh, Teruaki Takasaki
Summary: The RAF/MEK/ERK signaling pathway regulates various cellular processes and its activation is linked to cell proliferation and cancer. Further research on the mechanisms of ERK activation is essential for developing effective cancer treatments.
Review
Oncology
Eunus S. Ali, Shamima Akter, Sarker Ramproshad, Banani Mondal, Thoufiqul Alam Riaz, Muhammad Torequl Islam, Ishaq N. Khan, Anca Oana Docea, Daniela Calina, Javad Sharifi-Rad, William C. Cho
Summary: The MAPK pathway plays a crucial role in transmitting signals from outside the cell to inside, and is associated with cancer treatment response, normal cell pathway maintenance, and compensatory pathway activation. MAPK inhibitors often activate compensatory feedback loops, leading to resistance in tumor cells and microenvironment. Therefore, innovative combination therapies are needed to limit alternate pathway initiation.
CANCER CELL INTERNATIONAL
(2022)
Article
Oncology
Ying Zhang, Qian Lu, Nan Li, Ming Xu, Tatsuo Miyamoto, Jing Liu
Summary: Sulforaphane (SFN), a natural compound derived from broccoli, has been found to significantly inhibit migration and invasion of breast cancer cells by affecting cytoskeleton formation. SFN can also directly bind to RAF family proteins and inhibit phosphorylation of the signaling pathway. These findings suggest that SFN has the potential to be used as a therapeutic drug to inhibit breast cancer cell metastasis.
Article
Multidisciplinary Sciences
Ana Martin-Vega, Laura Ruiz-Peinado, Rocio Garcia-Gomez, Ana Herrero, Dalia de la Fuente-Vivas, Swetha Parvathaneni, Ruben Caloto, Marta Morante, Alex von Kriegsheim, Xose R. Bustelo, David B. Sacks, Berta Casar, Piero Crespo
Summary: RAS-ERK pathway signals are regulated by scaffold proteins, and it is revealed that scaffold proteins can interact with each other and undergo phosphorylation reactions. The trans-phosphorylation process participates in KSR1-regulated adipogenesis and the cytotoxicity exhibited by KSR-directed inhibitors. This finding has implications in signaling and the design of scaffold protein-aimed therapeutics.
