Functional profiling of p53 and RB cell cycle regulatory proficiency suggests mechanism-driven molecular stratification in endometrial carcinoma.

In the United States, Endometrial carcinoma (EC) is the most frequently occurring gynecologic cancer. Many ECs harbor mutations in cell cycle regulatory genes including TP53 and RB1, amongst others. RB and p53 both regulate the G1/S transition while p53 also regulates the G2/M transition and mitotic progression, all of which rely on targetable regulatory kinases.

Highly expressed VGLL3 in keloid fibroblasts promotes glycolysis and collagen production via the activation of Wnt/β-catenin signaling.

Purpose: This study investigated the effects and related mechanisms of Vestigial-like family member 3 (VGLL3) on keloid fibroblast (KF) proliferation, apoptosis, collagen production, and glycolysis.

Methods: Western blot, qRT-PCR, and immunohistochemistry were used for determining VGLL3 expression. KF viability, proliferation, and apoptosis were assessed using CCK-8 assay, EdU assay, and flow cytometry.

SPARC activates p38γ signaling to promote PFKFB3 protein stabilization and contributes to keloid fibroblast glycolysis.

Background: Keloids are currently challenging to treat because they recur after resection which may affect patients' quality of life. At present, no universal consensus on treatment regimen has been established. Thus, finding new molecular mechanisms underlying keloid formation is imminent.

Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata.

Unlabelled: Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown.

Human Cytomegalovirus Seropositivity and Viral DNA in Breast Tumors Are Associated with Poor Patient Prognosis.

Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0-100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes.

PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling.

Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. HCMV proteins and DNA are detected in tumors and metastases, suggesting an association with increased invasion. We investigated HCMV infection in human breast cancer cell lines compared to fibroblasts, a component of tumors, and the role of platelet-derived growth factor receptor-α (PDGFRα).

Latent Cytomegalovirus Infection in Female Mice Increases Breast Cancer Metastasis.

Cytomegalovirus (CMV) infects 40⁻70% of women, but infection has been reported in >95% of breast cancer patients. We investigated the consequences of these observations by infecting mice with mCMV or a negative control medium for 4 days, 11 days or 10 weeks to establish active, intermediate or latent infections, respectively. Syngeneic 4T1 or E0771 breast cancer cells were then injected into a mammary fat pad of BALB/c or C57BL/6 mice, respectively.

Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in adipose tissue: implications for the metabolic syndrome and breast cancer.

Lysophosphatidate (LPA) signaling through 6 receptors is regulated by the balance of LPA production by autotaxin (ATX) vs. LPA degradation by lipid phosphate phosphatases (LPPs). LPA promotes an inflammatory cycle by increasing the synthesis of cyclooxygenase-2 and multiple inflammatory cytokines that stimulate further ATX production.

Lysophosphatidate Signaling: The Tumor Microenvironment's New Nemesis.

Lysophosphatidate (LPA) is emerging as a potent mediator of cancer progression in the tumor microenvironment. Strategies for targeting LPA signaling have recently entered clinical trials for fibrosis. These therapies have potential to improve the efficacies of existing chemotherapies and radiotherapy by attenuating chronic inflammation, irrespective of diverse mutations within cancer cells.

Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy.

We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy.