Restoration treatments enhance tree growth and alter climatic constraints during extreme drought.

The frequency and severity of drought events are predicted to increase due to anthropogenic climate change, with cascading effects across forested ecosystems. Management activities such as forest thinning and prescribed burning, which are often intended to mitigate fire hazard and restore ecosystem processes, may also help promote tree resistance to drought. However, it is unclear whether these treatments remain effective during the most severe drought conditions or whether their impacts differ across environmental gradients.

Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma.

FAK inhibitors are in combinatorial clinical testing with agents that prevent Ras-Raf-MAPK pathway activation in various cancers. This study suggests that nuclear FAK limits ERK/MAPK activation in supporting HGSOC cell survival to cisplatin stress. Overall, it is likely that targets of FAK-mediated survival signaling may be tumor type- and context-dependent.

Declining ecological resilience and invasion resistance under climate change in the sagebrush region, United States.

In water-limited dryland ecosystems of the Western United States, climate change is intensifying the impacts of heat, drought, and wildfire. Disturbances often lead to increased abundance of invasive species, in part, because dryland restoration and rehabilitation are inhibited by limited moisture and infrequent plant recruitment events. Information on ecological resilience to disturbance (recovery potential) and resistance to invasive species can aid in addressing these challenges by informing long-term restoration and conservation planning.

Inducible FAK Deletion but not FAK Inhibition in Endothelial Cells Activates p53 to Suppress Tumor Growth in PYK2-null Mice.

Unlabelled: Focal adhesion kinase (FAK) functions as a signaling and scaffolding protein within endothelial cells (ECs) impacting blood vessel function and tumor growth. Interpretations of EC FAK-null phenotypes are complicated by related PYK2 (protein tyrosine kinase 2) expression, and to test this, we created PYK2 FAK mice with tamoxifen-inducible EC-specific Cre recombinase expression. At 11 weeks of age, EC FAK inactivation resulted in increased heart and lung mass and vascular leakage only on a PYK2 background.

Focal adhesion kinase signaling - tumor vulnerabilities and clinical opportunities.

Focal adhesion kinase (FAK; encoded by PTK2) was discovered over 30 years ago as a cytoplasmic protein tyrosine kinase that is localized to cell adhesion sites, where it is activated by integrin receptor binding to extracellular matrix proteins. FAK is ubiquitously expressed and functions as a signaling scaffold for a variety of proteins at adhesions and in the cell cytoplasm, and with transcription factors in the nucleus. FAK expression and intrinsic activity are essential for mouse development, with molecular connections to cell motility, cell survival and gene expression.

FAK, vinculin, and talin control mechanosensitive YAP nuclear localization.

Focal adhesions (FAs) are nanoscale complexes containing clustered integrin receptors and intracellular structural and signaling proteins that function as principal sites of mechanotransduction in part via promoting the nuclear translocation and activation of the transcriptional coactivator yes-associated protein (YAP). Knockdown of FA proteins such as focal adhesion kinase (FAK), talin, and vinculin can prevent YAP nuclear localization. However, the mechanism(s) of action remain poorly understood.

TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway.

Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance.

FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes.

Rationale: Vascular smooth muscle cells (SMCs) exhibit remarkable plasticity and can undergo dedifferentiation upon pathological stimuli associated with disease and interventions.

Objective: Although epigenetic changes are critical in SMC phenotype switching, a fundamental regulator that governs the epigenetic machineries regulating the fate of SMC phenotype has not been elucidated.

Methods And Results: Using SMCs, mouse models, and human atherosclerosis specimens, we found that FAK (focal adhesion kinase) activation elicits SMC dedifferentiation by stabilizing DNMT3A (DNA methyltransferase 3A).

Divergent climate change effects on widespread dryland plant communities driven by climatic and ecohydrological gradients.

Plant community response to climate change will be influenced by individual plant responses that emerge from competition for limiting resources that fluctuate through time and vary across space. Projecting these responses requires an approach that integrates environmental conditions and species interactions that result from future climatic variability. Dryland plant communities are being substantially affected by climate change because their structure and function are closely tied to precipitation and temperature, yet impacts vary substantially due to environmental heterogeneity, especially in topographically complex regions.

Endothelial angiogenic activity and adipose angiogenesis is controlled by extracellular matrix protein TGFBI.

Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM.

Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair.

How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads.

Targeting FAK in anticancer combination therapies.

Focal adhesion kinase (FAK) is both a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signalling and cell migration, but FAK can also promote cell survival in response to stress. FAK is commonly overexpressed in cancer and is considered a high-value druggable target, with multiple FAK inhibitors currently in development. Evidence suggests that in the clinical setting, FAK targeting will be most effective in combination with other agents so as to reverse failure of chemotherapies or targeted therapies and enhance efficacy of immune-based treatments of solid tumours.

FAK activity in cancer-associated fibroblasts is a prognostic marker and a druggable key metastatic player in pancreatic cancer.

Cancer-associated fibroblasts (CAFs) are considered the most abundant type of stromal cells in pancreatic ductal adenocarcinoma (PDAC), playing a critical role in tumour progression and chemoresistance; however, a druggable target on CAFs has not yet been identified. Here we report that focal adhesion kinase (FAK) activity (evaluated based on 397 tyrosine phosphorylation level) in CAFs is highly increased compared to its activity in fibroblasts from healthy pancreas. Fibroblastic FAK activity is an independent prognostic marker for disease-free and overall survival of PDAC patients (cohort of 120 PDAC samples).

Robust ecological drought projections for drylands in the 21st century.

Dryland ecosystems may be especially vulnerable to expected 21st century increases in temperature and aridity because they are tightly controlled by moisture availability. However, climate impact assessments in drylands are difficult because ecological dynamics are dictated by drought conditions that are difficult to define and complex to estimate from climate conditions alone. In addition, precipitation projections vary substantially among climate models, enhancing variation in overall trajectories for aridity.

Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring.

Soil and stand structure explain shrub mortality patterns following global change-type drought and extreme precipitation.

The probability of extreme weather events is increasing, with the potential for widespread impacts to plants, plant communities, and ecosystems. Reports of drought-related tree mortality are becoming more frequent, and there is increasing evidence that drought accompanied by high temperatures is especially detrimental. Simultaneously, extreme large precipitation events have become more frequent over the past century.

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in , and (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity.

Nuclear Focal Adhesion Kinase Controls Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Through GATA4-Mediated Cyclin D1 Transcription.

Rationale: Neointimal hyperplasia is characterized by excessive accumulation of vascular smooth muscle cells (SMCs) leading to occlusive disorders, such as atherosclerosis and stenosis. Blood vessel injury increases growth factor secretion and matrix synthesis, which promotes SMC proliferation and neointimal hyperplasia via FAK (focal adhesion kinase).

Objective: To understand the mechanism of FAK action in SMC proliferation and neointimal hyperplasia.

A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK.

Activating mutations in GNAQ/GNA11, encoding Gαq G proteins, are initiating oncogenic events in uveal melanoma (UM). However, there are no effective therapies for UM. Using an integrated bioinformatics pipeline, we found that PTK2, encoding focal adhesion kinase (FAK), represents a candidate synthetic lethal gene with GNAQ activation.

Adaptive Resistance to Chemotherapy, A Multi-FAK-torial Linkage.

Oncogenes provide tumor cells with a growth and survival advantage. Directed therapies targeted to oncogenic mutations (such as V600E) are part of effective late-stage melanoma treatment. However, tumors with V600E mutations, in approximately 10% of colorectal cancer, are generally treatment-insensitive.

Future soil moisture and temperature extremes imply expanding suitability for rainfed agriculture in temperate drylands.

The distribution of rainfed agriculture, which accounts for approximately ¾ of global croplands, is expected to respond to climate change and human population growth and these responses may be especially pronounced in water limited areas. Because the environmental conditions that support rainfed agriculture are determined by climate, weather, and soil conditions that affect overall and transient water availability, predicting this response has proven difficult, especially in temperate regions that support much of the world's agriculture. Here, we show that suitability to support rainfed agriculture in temperate dryland climates can be effectively represented by just two daily environmental variables: moist soils with warm conditions increase suitability while extreme high temperatures decrease suitability.

Multi-model comparison highlights consistency in predicted effect of warming on a semi-arid shrub.

A number of modeling approaches have been developed to predict the impacts of climate change on species distributions, performance, and abundance. The stronger the agreement from models that represent different processes and are based on distinct and independent sources of information, the greater the confidence we can have in their predictions. Evaluating the level of confidence is particularly important when predictions are used to guide conservation or restoration decisions.