Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death. Its overexpression in mouse renal cell carcinomas led to smaller tumor size with less tumor vascularization in a homograft tumor model. Mechanistically, HCaRG promotes de-phosphorylation of the proto-oncogene erythroblastosis oncogene B (ErbB)2/HER2 and epigenetic gene silencing of epidermal growth factor receptor and ErbB3 via promoter methylation. Extracellular signal-regulated kinase, AKT and mammalian target of rapamycin which mediate ErbB-dowstream signaling pathways are inactivated by HCaRG expression. In addition, HCaRG is underexpressed in human renal cell carcinomas and more expressed in normal tissue adjacent to renal cell carcinomas of patients with favorable prognosis. Taken together, our data suggest a role for HCaRG in the inhibition of tumor progression as a natural inhibitor of the ErbB signals in cancer and as a potential prognostic marker for renal cell carcinomas.

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Background/Aim: Copper metabolism MURR1 domain-containing 5 (COMMD5) is mainly expressed in renal tubules (RTs), where it facilitates re-differentiation of injured RTs. We reported that COMMD5 regulates the expression of epidermal growth factor receptor by participating in its endocytic membrane trafficking, thus inhibiting tumor growth.Here we aimed to determine the role of COMMD5 in malignant phenotypes of renal cell carcinoma (RCC). Materials and Methods: The associations between COMMD5 levels in RTs adjacent to RCC tumors in patients and their clinicopathologic characteristics were evaluated, and the effects of COMMD5 on cancer stemness in RCC cells were investigated. Results: Low COMMD5 levels in RTs correlated with high tumorigenesis and poor patient outcomes. COMMD5 overexpression in RCC cells reduced the proportion of cancer stem cell-like cells and their malignant phenotypes, including proliferation, invasion and sphere formation. Secreted COMMD5 from RT cells also reduced malignant phenotypes. Conclusion: COMMD5 might suppress malignant phenotypes of RCC, thus inhibiting tumor development and improving patient prognosis.Copper metabolism MURR1 domain-containing 5 (COMMD5), also known as hypertension-related, calcium-regulated gene, is characterized by a conserved COMM domain at its carboxyterminal end (1). Its expression is higher in the parathyroid and kidney of spontaneously hypertensive rats than in normotensive rats (2). Functional studies indicated that COMMD5 overexpression in kidney cells facilitates their differentiation, with a lower proliferative capacity (3). Overexpression of COMMD5 in proximal renal tubules (RTs) of mice accelerated tubular repair after acute kidney injury by facilitating redifferentiation of injured RT cells through the induction of P21 CIP1/WAF1 via a p53-independent pathway, resulting in faster recovery of renal function and a superior survival rate (4).Cancer afflicted about 18.1 million new patients worldwide in 2018 and accounted for nearly 9.6 million related deaths (5). Cancer morbidity and mortality are rapidly growing in every region of the world. The high mortality rate often correlates with a lack of clear symptoms, which results in late diagnosis for patients and the development of cancer resistant to chemotherapy and radiotherapy. Recent progress in cancer research has revealed that the presence of cancer stem cells (CSCs) is pivotal for the development of malignant phenotypes of various cancer types, including invasion, metastasis, recurrence and resistance to therapy (6-8). CSCs are small populations of cells that have the potential to reproduce and sustain cancer and the abilities of multiple differentiation and self-renewal (9, 10).Malignant kidney cancers afflict about 350,000 new patients worldwide, and the incidence of renal cell carcinoma (RCC) is increasing annually (11,12). Advanced kidney cancer in adults is resistant to conventional chemotherapy 2805 This article is freely accessible online.

We experienced a case of thyroid microcarcinoma with lymph node metastasis. A 68-year-old woman presented with the complaint of common cold-like symptoms. We performed chest CT. The CT showed no pneumonia, but multiple masses were seen in both lobes of the thyroid. The ultrasonography revealed multiple lesions in her thyroid. We performed aspiration biopsy cytology for these thyroid tumors. One tumor, located in the left lobe, 5 mm in diameter, was diagnosed as Class IV. The other tumors were diagnosed as Class II. Subtotal thyroidectomy with lymph nodes dissection (D1) was performed. The pathological diagnosis was papillary carcinoma of the thyroid with paratracheal lymph node metastasis. It is known that the prognosis of microcarcinoma of the thyroid is good. However, microcarcinoma of the thyroid with lymph node metastasis requires careful serial observations.