BET Inhibition Rescues Acinar-Ductal-Metaplasia and Ciliogenesis and Ameliorates Chronic Pancreatitis-Driven Changes in Mice With Loss of the Polarity Protein Par3.

Background & Aims: The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas injury and regeneration are poorly understood.

Methods: Cerulein-induced pancreatitis was induced in mice with conditional deletion of the polarity protein Par3 in the pancreas.

Co‑expression of and is associated with poor prognosis, and is required for the survival of ALDH1‑positive pancreatic cancer stem cells.

Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been identified as a prognostic marker in several types of cancer, including pancreatic cancer. However, to the best of our knowledge, the association between expression and cancer stem cell (CSC) markers, such as aldehyde dehydrogenase 1 (ALDH1), in pancreatic ductal adenocarcinoma (PDAC), and the role of in PDAC CSCs remains unclear. In the present study, a genomic dataset of primary pancreatic cancer (The Cancer Genome Atlas, Pan-Cancer Atlas) was downloaded and analyzed.

High Glucose-stimulated aPKC Activation Promotes Pancreatic Cancer Cell Progression Through YAP Signaling.

Background/aim: Persistent hyperglycemia caused by diabetes mellitus is a risk factor for pancreatic cancer (PC). We have previously reported that aberrant activation of atypical protein kinase C (aPKC) enhances PC cell progression. However, no reports have elucidated whether hyperglycemia promotes PC cell progression and whether aPKC activation is related to PC cell progression mechanisms.

High Expression Indicates Poor Prognosis in Prostate Cancer.

Background/aim: High expression of solute carrier family 20 member 1 (SLC20A1) indicates poor clinical outcomes for patients with breast cancer subtypes treated with endocrine therapy and radiotherapy. However, the association between SLC20A1 expression and clinical outcomes in prostate cancer remains to be determined.

Materials And Methods: Open-source datasets (The Cancer Genome Atlas prostate, Stand Up to Cancer-Prostate Cancer Foundation Dream Team, and The Cancer Genome Atlas PanCancer Atlas) were downloaded and analyzed.

High expression of PKCλ and ALDH1A3 indicates a poor prognosis, and PKCλ is required for the asymmetric cell division of ALDH1A3-positive cancer stem cells in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is the cancer with the poorest prognosis. One of the major properties reflecting its poor prognosis is high-grade heterogeneity, which leads to insensitivity to anticancer treatments. Cancer stem cells (CSCs) acquire phenotypic heterogeneity, generating abnormally differentiated cells by asymmetric cell division.

High Expression of and Predicts a Poor Prognosis in Basal-like Breast Cancer.

Background/aim: CD58 is an immune adhesion molecule on the cellular surface. It was previously found that a high expression of CD58 predicted a poor prognosis of patients with lower-grade gliomas. Therefore, the aim of this paper was to investigate the association between CD58 and breast cancer.

PAR3 restricts the expansion of neural precursor cells by regulating hedgehog signaling.

During brain development, neural precursor cells (NPCs) expand initially, and then switch to generating stage-specific neurons while maintaining self-renewal ability. Because the NPC pool at the onset of neurogenesis crucially affects the final number of each type of neuron, tight regulation is necessary for the transitional timing from the expansion to the neurogenic phase in these cells. However, the molecular mechanisms underlying this transition are poorly understood.

High SLC20A1 Expression Is Associated With Poor Prognosis for Radiotherapy of Estrogen Receptor-positive Breast Cancer.

Background/aim: Radiotherapy is one of the main treatments for estrogen receptor-positive (ER+) breast cancer. However, in some ER+ breast cancer cases, radiotherapy is insufficient to inhibit progression and there is a lack of markers to predict radiotherapy insensitivity. Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been proposed to be a viable prognostic marker for luminal A and B types of ER+ breast cancer.

High Expression of and Is Associated With Poor Prognosis in Luminal B Breast Cancer.

Background/aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear.

Materials And Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded.

High expression of SLC20A1 is less effective for endocrine therapy and predicts late recurrence in ER-positive breast cancer.

Estrogen receptor-positive (ER+) breast cancer intrinsically confers satisfactory clinical outcomes in response to endocrine therapy. However, a significant proportion of patients with ER+ breast cancer do not respond well to this treatment. Therefore, to evaluate the effects of endocrine therapy, there is a need for identification of novel markers that can be used at the time of diagnosis for predicting clinical outcomes, especially for early-stage and late recurrence.

GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival.

Background/aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs).

Materials And Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1 cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.

Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer.

Cancer cells upregulate the expression levels of glycolytic enzymes in order to reach the increased glycolysis required. One such upregulated glycolytic enzyme is glyoxalase 1 (GLO 1), which catalyzes the conversion of toxic methylglyoxal to nontoxic S-D-lactoylglutathione. Protein kinase Cλ (PKCλ) is also upregulated in various types of cancer and is involved in cancer progression.

Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles.

Hair follicles, mammalian mini-organs that grow hair, miniaturize during aging, leading to hair thinning and loss. Here we report that hair follicle stem cells (HFSCs) lose their regenerative capabilities during aging owing to the adoption of an atypical cell division program. Cell fate tracing and cell division axis analyses revealed that while HFSCs in young mice undergo typical symmetric and asymmetric cell divisions to regenerate hair follicles, upon aging or stress, they adopt an atypical 'stress-responsive' type of asymmetric cell division.

Phosphorylation and dephosphorylation of Ser852 and Ser889 control the clustering, localization and function of PAR3.

Cell polarity is essential for various asymmetric cellular events, and the partitioning defective (PAR) protein PAR3 (encoded by in mammals) plays a unique role as a cellular landmark to establish polarity. In epithelial cells, PAR3 localizes at the subapical border, such as the tight junction in vertebrates, and functions as an apical determinant. Although we know a great deal about the regulators of PAR3 localization, how PAR3 is concentrated and localized to a specific membrane domain remains an important question to be clarified.

High PKCλ expression is required for ALDH1-positive cancer stem cell function and indicates a poor clinical outcome in late-stage breast cancer patients.

Despite development of markers for identification of cancer stem cells, the mechanism underlying the survival and division of cancer stem cells in breast cancer remains unclear. Here we report that PKCλ expression was enriched in basal-like breast cancer, among breast cancer subtypes, and was correlated with ALDH1A3 expression (p = 0.016, χ2-test).

Shank2 Binds to aPKC and Controls Tight Junction Formation with Rap1 Signaling during Establishment of Epithelial Cell Polarity.

Epithelial cells establish apicobasal polarity by forming tight junctions (TJs) at the apical-lateral boundary, which play fundamental roles in physiological functions. An evolutionarily conserved atypical protein kinase C (aPKC)-partitioning defective (PAR) complex functions as a platform for TJ assembly during cell polarity establishment. However, how this complex converts the spatial cues into a subsequent active unit is unclear.

Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs.

Regnase-1-mediated mRNA decay (RMD), in which inflammatory mRNAs harboring specific stem-loop structures are degraded, is a critical part of proper immune homeostasis. Prior to initial translation, Regnase-1 associates with target stem-loops but does not carry out endoribonucleolytic cleavage. Single molecule imaging revealed that UPF1 is required to first unwind the stem-loops, thus licensing Regnase-1 to proceed with RNA degradation.

Atypical protein kinase C isoforms differentially regulate directional keratinocyte migration during wound healing.

Background: The epidermis possesses regenerative properties that become apparent only after wounding. Atypical protein kinase C (aPKC) isoforms aPKCζ and aPKCλ form a ternary complex with Par3 and Par6, and play crucial roles in establishing and maintaining epithelial cell polarity. The epidermal loss of aPKCλ results in progressive depletion of hair follicle stem cells.

aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA-binding ability.

Strict regulation of proliferation is vital for development, whereas unregulated cell proliferation is a fundamental characteristic of cancer. The polarity protein atypical protein kinase C lambda/iota (aPKCλ) is associated with cell proliferation through unknown mechanisms. In endothelial cells, suppression of aPKCλ impairs proliferation despite hyperactivated mitogenic signaling.

Atypical Protein Kinase C λ/ι Expression Is Associated with Malignancy of Oral Squamous Cell Carcinoma.

Background/aim: Atypical protein kinase C λ/ι (aPKCλ/ι) is a cell polarity-regulator localized in the tight junction and apical membrane in epithelial cells. Previous studies suggested that aPKCλ/ι overexpression and abnormal localization were involved in tumor progression in several cancers. We investigated the relationship between aPKCλ/ι and oral squamous cell carcinoma (OSCC).

Aberrant Nuclear Localization of aPKCλ/ι is Associated With Poorer Prognosis in Uterine Cervical Cancer.

We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples.

PAR-3 controls endothelial planar polarity and vascular inflammation under laminar flow.

Impaired cell polarity is a hallmark of diseased tissue. In the cardiovascular system, laminar blood flow induces endothelial planar cell polarity, represented by elongated cell shape and asymmetric distribution of intracellular organelles along the axis of blood flow. Disrupted endothelial planar polarity is considered to be pro-inflammatory, suggesting that the establishment of endothelial polarity elicits an anti-inflammatory response.

Increased oxytocin-monomeric red fluorescent protein 1 fluorescent intensity with urocortin-like immunoreactivity in the hypothalamo-neurohypophysial system of aged transgenic rats.

To visualize oxytocin in the hypothalamo-neurohypophysial system, we generated a transgenic rat that expresses the oxytocin-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In the present study, we examined the age-related changes of oxytocin-mRFP1 fluorescent intensity in the posterior pituitary (PP), the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of transgenic rats. The mRFP1 fluorescent intensities were significantly increased in the PP, the SON and the PVN of 12-, 18- and 24-month-old transgenic rats in comparison with 3-month-old transgenic rats.