Transcription cofactor Yes-associated protein (YAP) plays an important role in cancer progression. Here, we found that Aurora A kinase expression was positively correlated with YAP in lung cancer. Aurora A depletion suppresses lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. In addition, activation of Aurora A increases YAP protein abundance through maintaining its protein stability. Consistently, the transcriptional activity of YAP is increased upon Aurora A activation. We further showed that shAURKA suppressed YAP expression in the absence of Lats1/2, indicating that Aurora A regulates YAP independently of Hippo pathway. Instead, Aurora A induced blockage of autophagy to up-regulate YAP expression. Collectively, our findings provide insights into regulatory mechanisms of YAP expression in lung cancer development.
Various pathological processes are associated with the aberrant expression and function of cytokines, especially those belonging to the transforming growth factor-β (TGF-β) family. Nevertheless, the functions of members of the TGF-β family in cancer progression and therapy are still uncertain. Growth differentiation factor- 15, which exists in intracellular and extracellular forms, is classified as a divergent member of the TGF-β superfamily. It has been indicated that GDF-15 is also connected to the evolution of cancer both positively and negatively depending upon the cellular state and environment. Under normal physiological conditions, GDF-15 inhibits early tumour promotion. However, its abnormal expression in advanced cancers causes proliferation, invasion, metastasis, cancer stem cell formation, immune escape and a reduced response to therapy. As a clinical indicator, GDF-15 can be used as a tool for the diagnosis and therapy of an extensive scope of cancers. Although some basic functions of GDF-15 are noncontroversial, their mechanisms remain unclear and complicated at the molecular level. Therefore, GDF-15 needs to be further explored and reviewed.
Y-box binding protein 1 (YBX1) is involved in the development of multiple types of tumors. However, the relationship between YBX1 and autophagy in non-small cell lung cancer (NSCLC) remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and markers of autophagy (LC3I/II) in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC. The retrospective analysis of patients with NSCLC indicated that YBX1 was positively correlated with autophagy. Increased levels of YBX1 or autophagy also observed in NSCLC cells compared with those in 16HBE cells. Compared to the controls, the knockdown of YBX1 expression suppressed autophagy, increased drug sensitivity and promoted apoptosis in response to cisplatin in NSCLC cells by targeting the p110β promoter and inhibiting p110β/Vps34/beclin1 signaling pathways. We also demonstrated in an in vivo study that the overexpressed YBX1 effectively increased NSCLC growth and progression and decreased the sensitivity to cisplatin by inducing autophagy in a xenograft tumor model, and these effects were concomitant with the increasing of p110β and beclin1 expression. Collectively, these results show that YBX1 plays an essential role in autophagy in NSCLC.
Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.
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