The expression of galectin-1, one of the most important lectins participating in the malignant tumor development, has been shown to be regulated by hypoxia, but its exact mechanism remains elusive. Here, we find that ectopically expressed hypoxia-inducible factor (HIF) 1alpha protein, an oxygen-sensitive subunit of HIF-1 that is a master factor for cellular response to hypoxia, significantly increases galectin-1 expression in both messenger RNA and protein levels in all four colorectal cancer (CRC) cell lines tested. However, hypoxia-induced galectin-1 expression cannot be seen in sentrin/SUMO-specific protease 1 homozygous-null mouse embryonic fibroblasts that fail to accumulate HIF-1alpha protein. Furthermore, silence of HIF-1alpha or HIF-1beta expression by specific short hairpin RNAs (shRNAs) antagonizes hypoxia-induced galectin-1 expression. All these results propose that galectin-1 is a direct target of transcriptional factor HIF-1. Applying luciferase reporter assay and chromatin immunoprecipitation, we identify that two hypoxia-responsive elements located at -441 to -423 bp upstream to transcriptional start site of galectin-1 gene are essential for HIF-1-mediated galectin-1 expression. Finally, the knockdown of galectin-1 by its specific shRNA can significantly reduce hypoxia-induced invasion and migration of CRC cell line, and the ectopic expression of galectin-1 can remarkably restore invasion and migration abilities of HIF-1alpha-knocked SW620 cells, proposing that galectin-1 mediates the HIF-1-induced migration and invasion of CRC cells during hypoxia. Taken together, our results shed new light for understanding mechanism for hypoxia/HIF-1-mediated migration/invasion of CRC cells.

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Autophagy is a highly conserved, closely regulated homeostatic cellular activity that allows for the bulk degradation of long-lived proteins and cytoplasmic organelles. Its roles in cancer initiation and progression and in determining the response of tumor cells to anticancer therapy are complicated, and only limited investigation has been conducted on the potential significance of autophagy in the pathogenesis and therapeutic response of acute myeloid leukemia. Here we demonstrate that the inducible or transfected expression of the acute promyelocytic leukemia (APL)-specific PML-RARα, but not PLZF-RARα or NPM-RARα, fusion protein upregulates constitutive autophagy activation in leukemic and nonleukemic cells, as evaluated by hallmarks for autophagy including transmission electron microscopy. The significant increase in autophagic activity is also found in the leukemic cells-infiltrated bone marrow and spleen from PML-RARα-transplanted leukemic mice. The autophagy inhibitor 3-methyladenine significantly abrogates the autophagic events upregulated by PML-RARα, while the autophagic flux assay reveals that the fusion protein induces autophagy by increasing the on-rate of autophagic sequestration. Furthermore, this modulation of autophagy by PML-RARα is possibly mediated by a decreased activation of the Akt/mTOR pathway. Finally, we also show that autophagy contributes to the anti-apoptotic function of the PML-RARα protein. Given the critical role of the PML-RARα oncoprotein in APL pathogenesis, this study suggests an important role of autophagy in the development and treatment of this disease.

A novel Klebsiella pneumoniae strain (BPBA052) capable of degrading 3-phenoxybenzoic acid (3-PBA) was isolated from soybean rhizosphere soil. The strain was obtained by screening after enrichment, isolation, and purification using 3-PBA as the sole carbon and energy source. It could degrade 96.37% of 3-PBA (100 mg/L) within 72 h, and its growth and 3-PBA degradation followed kinetics models of logistic growth (XBPBA052 = 0.0883 × e0.0947t / [1 − 0.0792 × (1 − 0.0883 × e0.0947t)]; μm = 0.0947 h–1, X0 = 0.0883, and Xm = 1.1145) and first-order degradation (CBPBA052 = 101.8194 × e–0.0403t, k = 0.0403, t1/2 = 17.22 h), respectively. Based on Box–Behnken response surface analysis, the optimal temperature, pH, and 3-PBA concentration for K. pneumoniae BPBA052 were 35.01 °C, 7.77, and 150 mg/L, respectively. Moreover, pyrethroid pesticides (PPs) (such as β-cypermethrin, permethrin, bifenthrin, deltamethrin, and fenvalerate) and 3-PBA metabolites (including phenol, catechol, and protocatechuate) were efficiently utilized by BPBA052. We propose a novel microbial metabolic pathway for 3-PBA, based on metabolite identification; enzyme-degrading activity; and cloning of the phenol hydroxylase, catechol 1,2-dioxygenase, and protocatechuate 3,4-dioxygenase genes. This study provides a fundamental platform for further studies to reveal the mechanism of biodegradation of 3-BPA and show K. pneumoniae BPBA052 as a potential microbial resource for bioremediation of environments polluted with 3-PBA or PPs.