Targeted therapeutic strategies for Nectin-4 in breast cancer: Recent advances and future prospects.

Nectin-4 is a cell adhesion molecule which has gained more and more attention as a therapeutic target in cancer recently. Overexpression of Nectin-4 has been observed in various tumors, including breast cancer, and is associated with tumor progression. Enfortumab vedotin(EV)is an antibody-drug conjugate (ADC) targeting Nectin-4, which has been approved by FDA for the treatment of urothelial carcinoma.

Impaired cyclin D3 protein degradation contributes to trastuzumab resistance in HER2 positive breast cancer.

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance.

Targeting Trop-2 in cancer: Recent research progress and clinical application.

The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy.

Krüppel-like factors in breast cancer: Function, regulation and clinical relevance.

Breast cancer has accounted for the leading cause of cancer-related mortality among women worldwide. Although the progress in its diagnosis and treatment has come at a remarkable pace during the past several decades, there are still a wide array of problems regarding its progression, metastasis and treatment resistance that have not yet been fully clarified. Recently, an increasing number of studies have revealed that some members of Krüppel-like factors(KLFs) are significantly associated with cell proliferation, apoptosis, metastasis, cancer stem cell regulation and prognostic and predictive value for patients in breast cancer, indicating their promising prognostic and predictive potential for breast cancer survival and outcome.

CXXC4 activates apoptosis through up-regulating GDF15 in gastric cancer.

Worldwide, gastric cancer is one of the most fatal cancers. Epigenetic alterations in gastric cancer play important roles in silencing of tumor suppressor genes. We previously found that CXXC finger protein 4 (CXXC4) was a novel tumor suppressor in gastric cancer.

Hepatic Tmem30a Deficiency Causes Intrahepatic Cholestasis by Impairing Expression and Localization of Bile Salt Transporters.

Mutations in ATP8B1 or ATP11C (members of P4-type ATPases) cause progressive familial intrahepatic cholestasis type 1 in human or intrahepatic cholestasis in mice. Transmembrane protein 30A (TMEM30A), a β-subunit, is essential for the function of ATP8B1 and ATP11C. However, its role in the etiology of cholestasis remains poorly understood.

Regulation and role of post-translational modifications of enhancer of zeste homologue 2 in cancer development.

Post-translational modifications (PTMs) are critical molecular events which alter protein conformation after their synthesis and diversity protein properties by modulating their stability, localization, interacting partners or the activity of their substrates, consequently exerting pivotal roles in regulating the functions of many important eukaryotic proteins. It has been well acknowledged that PTMs are of great importance in a broad range of biological processes such as gene regulation, cell proliferation, differentiation and apoptosis, tissue development, diseases, tumor progression and drug resistance. As the core and contributing catalytic subunit of Polycomb repressive complex 2(PRC2), Enhancer of zeste homolog 2 (EZH2) is a master epigenetic regulator, often serving as a highly conserved histone methyltransferase (HMTase) to induce histone H3 lysine 27 trimethylation (H3K27me3) and repress gene transcription and expression.

Oncogenic Ras suppresses ING4-TDG-Fas axis to promote apoptosis resistance.

Ras is aberrantly activated in many cancers and active DNA demethylation plays a fundamental role to establish DNA methylation pattern which is of importance to cancer development. However, it was unknown whether and how Ras regulate DNA demethylation during carcinogenesis. Here we found that Ras downregulated thymine-DNA glycosylase (TDG), a DNA demethylation enzyme, by inhibiting the interaction of transcription activator ING4 with TDG promoter.

MicroRNAs as potential biomarkers in cancer: opportunities and challenges.

MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that posttranscriptionally regulate gene expression by targeting their corresponding messenger RNAs (mRNAs). Dysregulated miRNAs have been considered as a new type of ''oncomiRs" or ''tumor suppressors," playing essential roles in cancer initiation and progression. Using genome-wide detection methods, ubiquitously aberrant expression profiles of miRNAs have been identified in a broad array of human cancers, showing great potential as novel diagnostic and prognostic biomarkers of cancer with high specificity and sensitivity.

New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling.

As a well-characterized master player in epigenetic regulatory network, EZH2 is widely implicated in the development of many malignancies. We previously found that EZH2 promoted Wnt/β-catenin activation through downregulation of CXXC4 expression. In this report, we demonstrated that CXXC4 inhibited MAPK signaling through binding to ERK-1/2 and abrogating the interaction of ERK 1/2 with MEK1/2.

YY1-MIR372-SQSTM1 regulatory axis in autophagy.

Autophagy is a self-proteolytic process that degrades intracellular material to enable cellular survival under unfavorable conditions. However, how autophagy is activated in human carcinogenesis remains largely unknown. Herein we report an epigenetic regulation of autophagy in human cancer cells.

Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin.

Doxorubicin induces DNA damage to exert its anti-cancer function. Histone deacetylase 1 (HDAC1) can protect the genome from DNA damage. We found that doxorubicin specifically downregulates HDAC1 protein expression and identified HDAC1 as a target of miR-520h, which was upregulated by doxorubicin.

Regulation and function of mitophagy in development and cancer.

Beyond its role in recycling intracellular components nonselectively to sustain survival in response to metabolic stresses, autophagy can also selectively degrade specific cargoes such as damaged or dysfunctional organelles to maintain cellular homeostasis. Mitochondria, known as the power plant of cells, are the critical and dynamic organelles playing a fundamental role in cellular metabolism. Mitophagy, the selective autophagic elimination of mitochondria, has been identified both in yeast and in mammalian cells.

Annexin A6 is down-regulated through promoter methylation in gastric cancer.

Background: The aberrant activation of oncogenic signaling such as Ras/MAPK signaling is a frequent event in human cancers. In addition to genetic changes, epigenetic silencing of inhibitors in Ras/MAPK signaling contributes to the activation of Ras/MAPK signaling. Recently, ANXA6 has been shown to interact with Ras-GAP1 and inhibit Ras activation in human breast cancer.

MicroRNAs in hepatocellular carcinoma: regulation, function, and clinical implications.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Poor understanding of the mechanisms underlying the pathogenesis of HCC makes it difficult to be diagnosed and treated at early stage. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs of ~22 nucleotides in length, posttranscriptionally regulate gene expression by base pairing with the 3' untranslated regions (3'UTRs) of target messenger RNAs (mRNAs).

Histone deacetylase 3 inhibits expression of PUMA in gastric cancer cells.

During cancer development, tumor suppressor genes were silenced by promoter methylation or histone deacetylation. Histone deacetylases (HDACs) are important to maintain histone deacetylation. HDAC inhibitors (HDACis) were thus proposed as a new therapeutic approach to cancer.

Yin Yang-1 suppresses differentiation of hepatocellular carcinoma cells through the downregulation of CCAAT/enhancer-binding protein alpha.

As a member of the GLI-Kruppel family of transcriptional factors, Yin Yang-1 (YY1) functions as an oncogene in various types of cancers. However, the role of YY1 in hepatocellular carcinogenesis remains unknown. In this report, we investigated the relevance of YY1 to hepatocellular carcinoma (HCC) development.

Klotho is silenced through promoter hypermethylation in gastric cancer.

As one of major epigenetic changes to inactivate tumor suppressor genes in human carcinogenesis, promoter hypermethylation was proposed as a marker to define novel tumor suppressor genes and predict the prognosis of cancer patients. In the present study, we found KL (klotho) as a novel tumor suppressor gene silenced through promoter hypermethylation in gastric cancer, the second leading cause of cancer death worldwide. KL expression was downregulated in primary gastric carcinoma tissues (n=22, p<0.

Human mammaglobin: a superior marker for reverse-transcriptase PCR in detecting circulating tumor cells in breast cancer patients.

Breast cancer is the most frequent cancer in women in the USA and the second most common cause of death in females who develop cancer. Recently, the detection of circulating tumor cells has emerged as a promising tool for monitoring the progression of clinically occult micrometastases in breast cancer patients. Sensitive molecular techniques, primarily based upon the reverse-transcriptase PCR, using various molecules as markers, have been developed to detect circulating tumor cells.