AMPK: The energy sensor at the crossroads of aging and cancer.

AMP-activated protein kinase (AMPK) is a protein kinase that plays versatile roles in response to a variety of physiological stresses, including glucose deprivation, hypoxia, and ischemia. As a kinase with pleiotropic functions, it plays a complex role in tumor progression, exhibiting both tumor-promoting and tumor-suppressing activities. On one hand, AMPK enhances cancer cell proliferation and survival, promotes cancer metastasis, and impairs anti-tumor immunity.

Deregulated transcription factors in cancer cell metabolisms and reprogramming.

Metabolic reprogramming is an important cancer hallmark that plays a key role in cancer malignancies and therapy resistance. Cancer cells reprogram the metabolic pathways to generate not only energy and building blocks but also produce numerous key signaling metabolites to impact signaling and epigenetic/transcriptional regulation for cancer cell proliferation and survival. A deeper understanding of the mechanisms by which metabolic reprogramming is regulated in cancer may provide potential new strategies for cancer targeting.

AMPK: An odyssey of a metabolic regulator, a tumor suppressor, and now a contextual oncogene.

Metabolic reprogramming is a unique but complex biochemical adaptation that allows solid tumors to tolerate various stresses that challenge cancer cells for survival. Under conditions of metabolic stress, mammalian cells employ adenosine monophosphate (AMP)-activated protein kinase (AMPK) to regulate energy homeostasis by controlling cellular metabolism. AMPK has been described as a cellular energy sensor that communicates with various metabolic pathways and networks to maintain energy balance.

A reciprocal feedback loop between HIF-1α and HPIP controls phenotypic plasticity in breast cancer cells.

While phenotypic plasticity is a critical factor contributing to tumor heterogeneity, molecular mechanisms underlying this process are largely unknown. Here we report that breast cancer cells display phenotypic diversity in response to hypoxia or normoxia microenvironments by operating a reciprocal positive feedback regulation of HPIP and HIF-1α. We show that under hypoxia, HIF-1α induces HPIP expression that establishes cell survival, and also promotes cell migration/invasion, EMT and metastatic phenotypes in breast cancer cells.

Hematopoietic PBX-interacting protein is a novel regulator of mammary epithelial cell differentiation.

Hematopoietic PBX-interacting protein (HPIP, also known as PBXIP1) is an estrogen receptor (ER) interacting protein that regulates estrogen-mediated breast cancer cell proliferation and tumorigenesis. However, its functional significance in the context of mammary gland development is unexplored. Here, we report that HPIP is required for prolactin (PRL)-induced lactogenic differentiation in vitro.

HPIP protooncogene differentially regulates metabolic adaptation and cell fate in breast cancer cells under glucose stress via AMPK and RNF2 dependent pathways.

While cancer cells rewire metabolic pathways to sustain growth and survival under metabolic stress in solid tumors, the molecular mechanisms underlying these processes remain largely unknown. In this study, cancer cells switched from survival to death during the early to late phases of metabolic stress by employing a novel signaling switch from AMP activated protein kinase (AMPK)-Forkhead box O3 (FOXO3a)-hematopoietic PBX1-interacting protein (HPIP) to the ring finger protein 2 (RNF2)-HPIP-ubiquitin (Ub) pathway. Acute metabolic stress induced proto-oncogene HPIP expression in an AMPK-FOXO3a-dependent manner in breast cancer (BC) cells.

Zirconia-containing wollastonite ceramics derived from biowaste resources for bone tissue engineering.

Zirconia-containing wollastonite (CaSiO) ceramics with partial substitution of zirconia (1, 3 and 5 mol%) were prepared using eggshells and rice husk ash as source materials for calcium oxide and silica, respectively, through a sol-gel technique. The effect of incorporation of zirconia on in vitro bioactivity, mechanical properties, degradability and cytocompatibility of wollastonite was studied. Bioactivity was evaluated by in vitro assay using simulated body fluid while degradability was tested in Tris-HCl buffer solution for different time periods (1, 3, 7, 14 and 21 d) according to the ISO 10 993-14 standard.

Hematopoietic PBX-interacting protein is a substrate and an inhibitor of the APC/C-Cdc20 complex and regulates mitosis by stabilizing cyclin B1.

Proper cell division relies on the coordinated regulation between a structural component, the mitotic spindle, and a regulatory component, anaphase-promoting complex/cyclosome (APC/C). Hematopoietic PBX-interacting protein (HPIP) is a microtubule-associated protein that plays a pivotal role in cell proliferation, cell migration, and tumor metastasis. Here, using HEK293T and HeLa cells, along with immunoprecipitation and immunoblotting, live-cell imaging, and protein-stability assays, we report that HPIP expression oscillates throughout the cell cycle and that its depletion delays cell division.

Alpinoid c analog inhibits angiogenesis and induces apoptosis in COLO205 cell line.

Diarylheptanoids display an array of biological and pharmacological properties. We previously reported the synthesis of a diarylheptanoid Alpinoid c and a series of its derivatives, evaluated their cytotoxicity against various human cancer cells. We found some of these derivatives were significantly more potent than Alpinoid c in preventing the proliferation of various cancer cell lines.

Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents.

Two series of diaziridinyl quinone isoxazole derivatives were prepared and evaluated for their cytotoxic activity against MCF7, HeLa, BT549, A549 and HEK293 cell lines and interaction with tubulin. Compounds (6A-M: ) showed promising activity against all the 5 human cancer cell lines. Compounds 6A: , 6E: and 6 M: were potent [IC ranging between 2.

Bio-inspired synthesis of a hierarchical self-assembled zinc phosphate nanostructure in the presence of cowpea mosaic virus: in vitro cell cycle, proliferation and prospects for tissue regeneration.

Self-assembly is an important auto-organization process used in designing structural biomaterials which have the potential capability to heal tissues after traumatic injury. Although various materials having the ability to heal after injury are available, there is still a substantial need to develop new improved materials. To address this issue, we have developed hierarchical three-dimensional (3D) self-assembled zinc phosphate (Zn(PO)) in the presence of cowpea mosaic virus (CPMV).

MTA1 expression in human cancers - Clinical and pharmacological significance.

Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs.

Cytocompatibility studies of titania-doped calcium borosilicate bioactive glasses in-vitro.

The present study aims to elucidate the applications of Titania (TiO) doped calcium borosilicate glass as a biocompatible material in regenerative orthopedic applications. In this context, we have examined the bioactivity of various concentrations of TiO doped glasses with the help of simulated body fluid (SBF). Cytocompatibility, cell proliferation, and protein expression studies revealed the potential candidature of TiO doped glasses on osteoblast cell lines (MG-63).

HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation.

Purpose: Hematopoietic PBX interacting protein (HPIP), a scaffold protein, is known to regulate the proliferation, migration and invasion in different cancer cell types. The aim of this study was to assess the role of HPIP in ovarian cancer cell migration, invasion and epithelial-mesenchymal transition (EMT), and to unravel the mechanism by which it regulates these processes.

Methods: HPIP expression was assessed by immunohistochemistry of tissue microarrays containing primary ovarian tumor samples of different grades.