The cellular response to hypoxia is regulated by hypoxia-inducible factor-1α and -2α (HIF-1α and -2α). We have discovered that filamin A (FLNA), a large cytoskeletal actin-binding protein, physically interacts with HIF-1α and promotes tumor growth and angiogenesis. Hypoxia induces a calpain-dependent cleavage of FLNA to generate a naturally occurring C-terminal fragment that accumulates in the ...

Introduction: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer made up of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. Under hypoxic conditions, HIF-1α is stabilized and binds to hypoxia response elements that act as transcriptional controls of several genes. Among the 70 target genes of HIF-1 known so far, several are involved in angiogenesis, cell proli...

BACKGROUND Hypoxia inducible factors (HIFs) are the principal means by which cells upregulate genes in response to hypoxia and certain other stresses. There are two major HIFs, HIF-1 and HIF-2. We previously found that certain genes are preferentially activated by HIF-2. One was protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1). PTPRZ1 is overexpressed in a number of tumors ...

The etiology of most chronic angiogenic diseases such as rheumatoid arthritis, atherosclerosis, diabetes complications, and cancer includes the presence of pockets of hypoxic cells growing behind aerobic cells and away from blood vessels. Hypoxic cells are the result of uncontrolled growth and insufficient vascularization and have undergone a shift from aerobic to anaerobic metabolism. Cells re...

Inactivating mutations of the von Hippel-Lindau (VHL) tumor suppressor gene are associated with inherited VHL syndrome, which is characterized by susceptibility to a variety of neoplasms, including central nervous system hemangioblastoma and clear cell renal cell carcinoma (CCRCC). Mutations in the VHL gene are also found in the majority of sporadic clear cell renal carcinoma, the most common m...

Hypoxia-inducible factor-1alpha (HIF-1alpha) induces tumor proliferation, angiogenesis and metastasis. Reactive oxygen species, hypoxia, and growth factor stimulation induce HIF-1alpha, and the augmented HIF-1alpha activity confers upon cancer cells the ability to adapt to microenvironments. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth...

BACKGROUND Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1alpha concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1alpha overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells. AIMS To in...

Hypoxia-inducible factor-1α (HIF-1α) induces tumor proliferation, angiogenesis and metastasis. Reactive oxygen species, hypoxia, and growth factor stimulation induce HIF-1α, and the augmented HIF-1α activity confers upon cancer cells the ability to adapt to microenvironments. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. Nonetheless, t...

PURPOSE Solid tumors encounter a growth-limiting hypoxic microenvironment as they develop. Hypoxia-inducible factors (HIF) play important roles in hypoxia-associated tumor development and therapeutic resistance. Targeting the HIF pathway (especially HIF-1α) represents a promising cancer treatment strategy. Here, we report a novel class of HIF-1α inhibitors and the possible molecular basis of in...

Recent evidence established a crucial role for mammalian oxygen sensing transcription factor hypoxia inducible factor-1 (HIF-1) in innate immunity against intracellular pathogens. In response to most of these pathogens host phagocytes increase transcription of HIF-1α, the regulatory component of HIF-1 to express various effector molecules against invaders. Leishmania donovani (LD), a protozoan ...