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

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.

Morphological and physiological responses of cotton (Gossypium hirsutum L.) plants to salinity.

Salinization usually plays a primary role in soil degradation, which consequently reduces agricultural productivity. In this study, the effects of salinity on growth parameters, ion, chlorophyll, and proline content, photosynthesis, antioxidant enzyme activities, and lipid peroxidation of two cotton cultivars, [CCRI-79 (salt tolerant) and Simian 3 (salt sensitive)], were evaluated. Salinity was investigated at 0 mM, 80 mM, 160 mM, and 240 mM NaCl for 7 days. Salinity induced morphological and physiological changes, including a reduction in the dry weight of leaves and roots, root length, root volume, average root diameter, chlorophyll and proline contents, net photosynthesis and stomatal conductance. In addition, salinity caused ion imbalance in plants as shown by higher Na+ and Cl- contents and lower K+, Ca2+, and Mg2+ concentrations. Ion imbalance was more pronounced in CCRI-79 than in Simian3. In the leaves and roots of the salt-tolerant cultivar CCRI-79, increasing levels of salinity increased the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR), but reduced catalase (CAT) activity. The activities of SOD, CAT, APX, and GR in the leaves and roots of CCRI-79 were higher than those in Simian 3. CAT and APX showed the greatest H2O2 scavenging activity in both leaves and roots. Moreover, CAT and APX activities in conjunction with SOD seem to play an essential protective role in the scavenging process. These results indicate that CCRI-79 has a more effective protection mechanism and mitigated oxidative stress and lipid peroxidation by maintaining higher antioxidant activities than those in Simian 3. Overall, the chlorophyll a, chlorophyll b, and Chl (a+b) contents, net photosynthetic rate and stomatal conductance, SOD, CAT, APX, and GR activities showed the most significant variation between the two cotton cultivars.