Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma.

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features.

YAP1 controls the N-cadherin-mediated tumor-stroma interaction in melanoma progression.

The hallmark of epithelial-to-mesenchymal transition (EMT) is the switch from epithelial cadherin (E-cadherin) to neural cadherin (N-cadherin), allowing melanoma cells to form a homotypic N-cadherin-mediated adhesion with stromal fibroblasts. However, how cadherin switching is initiated, maintained, and regulated in melanoma remains elusive. Here, we report a novel mechanism underlying cadherin switching in melanoma cells that is regulated by stromal Yes-associated protein 1 (YAP1) signaling.

The MprF homolog LysX synthesizes lysyl-diacylglycerol contributing to antibiotic resistance and virulence.

Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago in , but the biosynthetic pathway and function of this aminoacylated lipid have since remained uncharacterized. Combining genetic methods, mass spectrometry, and biochemical approaches, we show that the multiple peptide resistance factor (MprF) homolog LysX from and two mycobacterial species is responsible for Lys-DAG synthesis. LysX is conserved in most Actinobacteria and was previously implicated in the synthesis of another modified lipid, lysyl-phosphatidylglycerol (Lys-PG), in .

YAP1 controls the N-cadherin-mediated tumor-stroma interaction in melanoma progression.

Epithelial-to-mesenchymal transition (EMT) is crucial for melanoma cells to escape keratinocyte control, invade underlying dermal tissues, and metastasize to distant organs. The hallmark of EMT is the switch from epithelial cadherin (E-cadherin) to neural cadherin (N-cadherin), allowing melanoma cells to form a homotypic N-cadherin-mediated adhesion with stromal fibroblasts. However, how "cadherin switching" is initiated, maintained, and regulated in melanoma remains unknown.

Precancerous Lesions of the Head and Neck Region and Their Stromal Aberrations: Piecemeal Data.

Head and neck squamous cell carcinomas (HNSCCs) develop through a series of precancerous stages from a pool of potentially malignant disorders (PMDs). Although we understand the genetic changes that lead to HNSCC, our understanding of the role of the stroma in the progression from precancer to cancer is limited. The stroma is the primary battleground between the forces that prevent and promote cancer growth.

The dermal papilla dilemma and potential breakthroughs in bioengineering hair follicles.

The generation and growing of de novo hair follicles is the most daring hair replacement approach to treat alopecia. This approach has been explored at least since the 1960s without major success. Latest in the 1980s, the realization that the mesenchymal compartment of hair follicles, the dermal papilla (DP), is the crucial signaling center and element required for fulfilling this vision of hair follicle engineering, propelled research into the fibroblasts that occupy the DP.

The origins of skin diversity: lessons from dermal fibroblasts.

Skin is largely composed of an epidermis that overlies a supporting dermis. Recent advancements in our understanding of how diverse groups of dermal fibroblasts regulate epidermal and hair follicle growth and differentiation have been fueled by tools capable of resolving molecular heterogeneity at a single-cell level. Fibroblast heterogeneity can be traced back to their developmental origin before their segregation into spatially distinct fibroblast subtypes.

Augmented CPT1A Expression Is Associated with Proliferation and Colony Formation during Barrett's Tumorigenesis.

Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett's Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma.

Anticancer function of microRNA-30e is mediated by negative regulation of HELLPAR, a noncoding macroRNA, and genes involved in ubiquitination and cell cycle progression in prostate cancer.

Prostate cancer (PCa) progression relies on androgen receptor (AR) function, making AR a top candidate for PCa therapy. However, development of drug resistance is common, which eventually leads to development of castration-resistant PCa. This warrants a better understanding of the pathophysiology of PCa that facilitates the aberrant activation of key signaling pathways including AR.

ATP13A3 facilitates polyamine transport in human pancreatic cancer cells.

The purpose of this study is to provide an increased understanding of the molecular mechanisms responsible for mammalian polyamine transport, a process that has been a long-standing 'black box' for the polyamine field. Here, we describe how ATP13A3, a P-type ATPase, functions as a polyamine transporter in response to different polyamine stimuli and polyamine-targeted therapies in highly proliferating pancreatic cancer cells. We assessed the expression, cellular localization and the response of the human ATP13A3 protein to polyamine treatments in different pancreatic cancer cell lines using Western blot and immunofluorescence microscopy.

BRAF Inhibitors Reprogram Cancer-Associated Fibroblasts to Drive Matrix Remodeling and Therapeutic Escape in Melanoma.

The tumor stroma and its cellular components are known to play an important role in tumor response to treatment. Here, we report a novel resistance mechanism in melanoma that is elicited by BRAF inhibitor (BRAFi)-induced noncanonical activation of nuclear β-catenin signaling in cancer-associated fibroblasts (CAF). Treatment with BRAFi leads to an expanded CAF population with increased β-catenin nuclear accumulation and enhanced biological properties.

LncRNA PAINT is associated with aggressive prostate cancer and dysregulation of cancer hallmark genes.

Long noncoding RNAs (lncRNAs) play regulatory role in cellular processes and their aberrant expression may drive cancer progression. Here we report the function of a lncRNA PAINT (prostate cancer associated intergenic noncoding transcript) in promoting prostate cancer (PCa) progression. Upregulation of PAINT was noted in advanced stage and metastatic PCa.

UBXN7 cofactor of CRL3 and CRL2 ubiquitin ligase complexes mediates reciprocal regulation of NRF2 and HIF-1α proteins.

UBXN7 is a cofactor protein that provides a scaffold for both CRL3 and CRL2 ubiquitin ligase complexes involved in the regulation of the NRF2 and HIF-1α protein levels respectively. NRF2 and HIF-1α are surveillance transcription factors that orchestrate the cellular response to oxidative stress (NRF2) or to hypoxia (HIF-1α). Since mitochondria are the main oxygen sensors as well as the principal producers of ROS, it can be presumed that they may be able to modulate the activity of CRL3 and CRL2 complexes in response to stress.

Author Correction: MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MicroRNAs as Guardians of the Prostate: Those Who Stand before Cancer. What Do We Really Know about the Role of microRNAs in Prostate Biology?

Prostate cancer is the second leading cause of cancer-related deaths of men in the Western world. Despite recent advancement in genomics, transcriptomics and proteomics to understand prostate cancer biology and disease progression, castration resistant metastatic prostate cancer remains a major clinical challenge and often becomes incurable. MicroRNAs (miRNAs), about 22-nucleotide-long non-coding RNAs, are a group of regulatory molecules that mainly work through post-transcriptional gene silencing via translational repression.

Multifaceted Function of MicroRNA-299-3p Fosters an Antitumor Environment Through Modulation of Androgen Receptor and VEGFA Signaling Pathways in Prostate Cancer.

Prostate cancer (PCa) is one of the most common cancers to affect men worldwide. Androgen receptor (AR) signaling is central to PCa and PCa therapy. MicroRNAs (miRNAs) play crucial roles in the regulation of prostate cancer through modulation of signaling pathways.

Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1α) and metabolic reprogramming by modulating the UBXN7 cofactor protein.

MUL1 is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with its RING finger domain facing the cytoplasm. MUL1 participates in various biological pathways involved in apoptosis, mitochondrial dynamics, and innate immune response. The unique topology of MUL1 enables it to "sense" mitochondrial stress in the intermembrane mitochondrial space and convey these signals through the ubiquitination of specific cytoplasmic substrates.

The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts.

β-catenin is a multifunctional protein that plays crucial roles in embryonic development, physiological homeostasis, and a wide variety of human cancers. Previously, we showed that in vivo targeted ablation of β-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth. However, when the expression of β-catenin was ablated in melanoma-associated fibroblasts before tumor initiation, melanoma development was surprisingly accelerated.

Divide and conquer: two stem cell populations in squamous epithelia, reserves and the active duty forces.

Stem cells are of great interest to the scientific community due to their potential role in regenerative and rejuvenative medicine. However, their role in the aging process and carcinogenesis remains unclear. Because DNA replication in stem cells may contribute to the background mutation rate and thereby to cancer, reducing proliferation and establishing a relatively quiescent stem cell compartment has been hypothesized to limit DNA replication-associated mutagenesis.

N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against PAO1.

Nosocomial infections pose serious health concerns with over 2 million reported annually in the United States. Many of these infections are associated with bacterial resistance to antibiotics and hence, alternative treatments are critically needed. The objective of this study was to assess the antimicrobial efficacy of a gallium (Ga)-based particle coated with N-Acetyl Cysteine (Ga-NAC) against PAO1.

Activin A-mediated epithelial de-differentiation contributes to injury repair in an in vitro gastrointestinal reflux model.

Reflux esophagitis is a result of esophageal exposure to acid and bile during episodes of gastroesophageal reflux. Aside from chemical injury to the esophageal epithelium, it has been shown that acid and bile induce cytokine-mediated injury by stimulating the release of pro-inflammatory cytokines. During the repair and healing process following reflux injury, the squamous esophageal cells are replaced with a columnar epithelium causing Barrett's metaplasia, which predisposes patients to esophageal adenocarcinoma.

3D porous chitosan-alginate scaffold stiffness promotes differential responses in prostate cancer cell lines.

Prostate cancer (PCa) is a leading cause of death for men worldwide. Most PCa patients die from metastasis and bone is the most common metastatic site. Three dimensional (3D) porous chitosan-alginate (CA) scaffolds were developed for bone tissue engineering and demonstrated for culture of cancer cells and enrichment of cancer stem cells.

Cancer-Associated Fibroblasts Build and Secure the Tumor Microenvironment.

Tumor cells reside in a highly complex and heterogeneous tumor microenvironment (TME), which is composed of a myriad of genetically stable non-cancer cells, including fibroblasts, immune cells, endothelial cells, and epithelial cells, and a tumor-specific extracellular matrix (ECM). Cancer-associated fibroblasts (CAFs), as an abundant and active stromal cell population in the TME, function as the signaling center and remodeling machine to aid the creation of a desmoplastic tumor niche. Although there is no denial that the TME and CAFs may have anti-tumor effects as well, a great deal of findings reported in recent years have convincingly revealed the tumor-promoting effects of CAFs and CAF-derived ECM proteins, enzymes, chemical factors and other downstream effectors.

Expression of FGD4 positively correlates with the aggressive phenotype of prostate cancer.

Background: FGD4 (Frabin) is an F-actin binding protein with GTP/GDP exchange activity specific for CDC42. It is involved in reorganization of the actin cytoskeleton, which requires both actin binding and CDC42 activating function of FGD4. Expression of FGD4 is altered in patients with heterogeneous hereditary motor and sensory neuropathies as a result of demyelination of peripheral nerves.