KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway.

KDF1 has been reported to be correlated with carcinogenesis. However, its role and mechanism are far from clear. To explore the possible role and underlying mechanism of KDF1 in lung adenocarcinoma (LUAD), we investigated KDF1 expression in LUAD tissues and the influence of KDF1 in the phenotype of LUAD cells (A549 and PC-9) as well as the underlying mechanism. Compared to non-tumor lung epithelial cells, KDF1 was upregulated in the cancer cells of the majority of LUAD patients, and its expression was correlated with tumor size. Patients with enhanced KDF1 in cancer cells (compared with paired adjacent non-neoplastic lung epithelial cells) had shorter overall survival than patients with no increased KDF1 in cancer cells. Knockdown of KDF1 inhibited the migration, proliferation and invasion of LUAD cells in vitro. And overexpression of KDF1 increased the growth of the subcutaneous tumors in mice. In terms of molecular mechanisms, overexpression of KDF1 induced the expression of AKT, p-AKT and p-STAT3. In KDF1-overexpressing A549 cells, inhibition of the STAT3 pathway decreased the level of AKT and p-AKT, whereas inhibition of the AKT pathway had no effect on the activation of STAT3. Inhibition of STAT3 or AKT pathways reversed the promoting effects of KDF1 overexpression on the LUAD cell phenotype and STAT3 inhibition appeared to have a better effect. Finally, in the cancer cells of LUAD tumor samples, the KDF1 level was observed to correlate positively with the level of p-STAT3. All these findings suggest that KDF1, which activates STAT3 and the downstream AKT pathway in LUAD, acts as a tumor-promoting factor and may represent a therapeutic target.

Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy.

The transforming growth factor (TGF)-ß signaling pathway controls many cellular processes, including proliferation, differentiation, and apoptosis. Abnormalities in the TGF-ß signaling pathway and its components are closely related to the occurrence of many human diseases, including cancer. Mothers against decapentaplegic homolog 4 (Smad4), also known as deleted in pancreatic cancer locus 4, is a typical tumor suppressor candidate gene locating at q21.1 of human chromosome 18 and the common mediator of the TGF-ß/Smad and bone morphogenetic protein/Smad signaling pathways. It is believed that Smad4 inactivation correlates with the development of tumors and stem cell fate decisions. Smad4 also interacts with cytokines, miRNAs, and other signaling pathways, jointly regulating cell behavior. However, the regulatory function of Smad4 in tumorigenesis, stem cells, and drug resistance is currently controversial. In addition, Smad4 represents an attractive therapeutic target for cancer. Elucidating the specific role of Smad4 is important for understanding the mechanism of tumorigenesis and cancer treatment. Here, we review the identification and characterization of Smad4, the canonical TGF-ß/Smad pathway, as well as the multiple roles of Smad4 in tumorigenesis, stem cells, and drug resistance. Furthermore, we provide novel insights into the prospects of Smad4-targeted cancer therapy and the challenges that it will face in the future.

Effects of exogenous Ca2+ on stomatal traits, photosynthesis, and biomass of maize seedings under salt stress.

Understanding the responses of stomatal structure, photosynthesis and biomass of maize to exogenous Ca2+ addition under NaCl stress has important significance for further uncovering the alleviative mechanism of exogenous Ca2+ on maize under salt stress. We examined the effects of exogenous Ca2+(0, 5, 10, 20, 40, 80 mmol·L-1) on the stomatal structure, photosynthesis and biomass of maize (Zea mays L. cv. Jingke 665) seedlings under NaCl stress (100 mmol·L-1). Our results showed that exogenous Ca2+ addition had limited effect on stomatal density, but significantly decreased stomatal shape index, stomatal area, stomatal length, stomatal width, and stomatal cir-cumference. Meanwhile, the net photosynthetic rate (Pn) initially increased and then decreased with the increases of exogenous Ca2+ concentration, whereas both the stomatal conductance (gs) and intercellular CO2 concentration (Ci) were decreased, suggesting that the decrease of Pn was mainly due to stomatal limitation under high Ca2+ concentration. The biomass of maize seedlings was increased and the root/shoot ratio was decreased with the increases of exogenous Ca2+ concentration, suggested that the alleviated effect of exogenous Ca2+ on aboveground biomass was higher than that on belowground biomass of maize under salt stress.