scholarly journals RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics

2020 ◽  
Vol 477 (15) ◽  
pp. 2893-2919
Author(s):  
Walaa E. Kattan ◽  
John F. Hancock
Keyword(s):  
Plasma Membrane ◽  
Cell Growth ◽  
Cancer Cells ◽  
Special Focus ◽  
Ras Proteins ◽  
Membrane Interactions ◽  
Multiple Methods ◽  
Membrane Biology ◽  
The Past ◽  
Cell Growth And Proliferation

The three human RAS proteins are mutated and constitutively activated in ∼20% of cancers leading to cell growth and proliferation. For the past three decades, many attempts have been made to inhibit these proteins with little success. Recently; however, multiple methods have emerged to inhibit KRAS, the most prevalently mutated isoform. These methods and the underlying biology will be discussed in this review with a special focus on KRAS-plasma membrane interactions.

scholarly journals Exploiting cancer vulnerabilities: mTOR, autophagy, and homeostatic imbalance

2017 ◽  
Vol 61 (6) ◽  
pp. 699-710 ◽  
Author(s):  
Charlotte E. Johnson ◽  
Andrew R. Tee
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Energy Homeostasis ◽  
Cellular Stress ◽  
Growth Control ◽  
Potential Therapeutic Target ◽  
Wide Range ◽  
Cell Growth And Proliferation ◽  
Mtor Complex 1 ◽  
Cell Growth Control

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) at lysosomes plays a pivotal role in cell growth control where an array of large multiprotein complexes relay nutrient, energy, and growth signal inputs through mTORC1. In cancer cells, such regulation often becomes disconnected, leading to uncontrolled cell growth and an elevation in cellular stress. Consequently, cancer cells often lose homeostatic balance as they grow in unfavorable conditions, i.e. when nutrients and energy are limited yet mTORC1 is still aberrantly activated. Cancer cells lose signaling flexibility because of hyperactive mTORC1 that leads to heightened cellular stress and loss of nutrient and energy homeostasis, all of which are potential avenues for cancer therapy. Cancer cells often enhance mTORC1 to drive cell growth and proliferation, while also maintaining their survival. Autophagy regulation by mTORC1 is critically involved in nutrient and energy homeostasis, cell growth control, and survival. Studying mTORC1 and autophagy as a potential therapeutic target for cancer treatment has been the focus of a wide range of research over the past few decades. This review will explore the signaling pathways central to mTORC1 and autophagy regulation, and cancer vulnerabilities while considering anticancer therapies.

Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors

2019 ◽  
Vol 19 (23) ◽  
pp. 2114-2127 ◽  
Author(s):  
Na Ye ◽  
Qingfeng Xu ◽  
Wanwan Li ◽  
Pingyuan Wang ◽  
Jia Zhou
Keyword(s):  
Plasma Membrane ◽  
Cell Growth ◽  
High Throughput Screening ◽  
Drug Repurposing ◽  
Membrane Localization ◽  
Clinical Use ◽  
Ras Proteins ◽  
Plasma Membrane Localization ◽  
Recent Advances ◽  
Specific Inhibitors

: The Ras proteins play an important role in cell growth, differentiation, proliferation and survival by regulating diverse signaling pathways. Oncogenic mutant K-Ras is the most frequently mutated class of Ras superfamily that is highly prevalent in many human cancers. Despite intensive efforts to combat various K-Ras-mutant-driven cancers, no effective K-Ras-specific inhibitors have yet been approved for clinical use to date. Since K-Ras proteins must be associated to the plasma membrane for their function, targeting K-Ras plasma membrane localization represents a logical and potentially tractable therapeutic approach. Here, we summarize the recent advances in the development of K-Ras plasma membrane localization inhibitors including natural product-based inhibitors achieved from high throughput screening, fragment-based drug design, virtual screening, and drug repurposing as well as hit-to-lead optimizations.

MAP KINASE SIGNALING PATHWAYS DIFFERENTIALLY AFFECT CELL GROWTH AND PROLIFERATION OF INVASIVE BLADDER CANCER CELLS

2009 ◽  
Vol 181 (4S) ◽  
pp. 344-344
Author(s):  
Jane Peterson ◽  
Binod Kumar ◽  
Sweaty Koul ◽  
Lakshmipathi Khandrika ◽  
Shandra Wilson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Growth ◽  
Map Kinase ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Invasive Bladder Cancer ◽  
Kinase Signaling ◽  
Bladder Cancer Cells ◽  
Cell Growth And Proliferation ◽  
Affect Cell Growth
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