Yen-Nien Liu

Taipei Medical University | TMU

Prostate cancer (PCa) is one of the most prevalent cancers in men, yet its pathogenic pathways remain poorly understood. Transcriptomics and high-throughput sequencing can help uncover cancer diagnostic targets and understand biological circuits. Using prostate adenocarcinoma (PRAD) datasets of various web-based applications (GEPIA, UALCAN, cBioPor...

Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical impl...

Androgen deprivation therapy (ADT)-induced neuroendocrine differentiation (NED) is a well-known lethal subtype of prostate cancer (PCa) with a median survival rate of less than one year. Despite the increasing research attention on this variant of PCa, the underlying mechanism orchestrating therapy-related neuroendocrine prostate cancer (NEPC) rema...

Conventional treatment of prostate cancer (PCa) uses androgen deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to AR-negative phenotype with neuroendocrine (NE) features on histology, which is associated with metabolic disturbances and poor prognosis. However, th...

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However,...

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men worldwide. Despite the presence of accumulated clinical strategies for PCa management, limited prognostic/sensitive biomarkers are available to follow up on disease occurrence and progression. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression throu...

Neuroendocrine differentiation (NED) frequently occurs in androgen-deprivation therapy (ADT)-resistant prostate cancer (PCa) and is typically associated with metabolic pathway alterations, acquisition of lineage plasticity, and malignancy. There is no conventional therapeutic approach for PCa patients with NED pathologic features because the molecu...

Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled. By unbiased...

Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT signaling promotes activation of cytokine signaling and contri...

Prostate cancer (PCa) is one of the most common cancers in the world and causes thousands of deaths every year. Conventional therapy for PCa includes surgery and androgen deprivation therapy (ADT). However, about 10–20% of all PCa cases relapse; there is also the further development of castration resistant adenocarcinoma (CRPC-Adeno) or neuroendocr...

Neuroendocrine (NE) differentiation is a well-recognized phenotypic change of prostate cancer after androgen-deprivation therapy (ADT) that ultimately develops an aggressive subtype. An increasing number of patients with NE histologic type prostate cancer present with metabolic genes disorder. However, the metabolic pathways that influence the mali...

Nerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcrip...

Neuroendocrine (NE) differentiation is a well-recognized phenotypic change of prostate cancer after androgen deprivation therapy (ADT), and it ultimately develops into an aggressive subset of this disease. However, the contribution of signaling pathways that lead to metabolic disorders and NE differentiation of prostate cancer remains unclear. In t...

p>The current therapies for prostate cancer, which can either be androgen-sensitive or androgen-insensitive ones, are based on AR-targeting approaches; however, there is no available treatment for neuroendocrine prostate cancer (NEPC). We previously identified the leukemia inhibitory factor (LIF), which is stimulated by androgen deprivation therapy...

Purpose: The molecular targets for castration-resistant prostate cancer (CRPC) are unknown because the disease inevitably recurs, and therapeutic approaches for patients with CRPC remain less well understood. We sought to investigate regulatory mechanisms that result in increased therapeutic resistance, which is associated with neuroendocrine diff...

Retinoids are vitamin A derivatives that regulate crucial biological processes such as cellular proliferation, apoptosis, and differentiation. The use of natural retinoids in cancer therapy is limited due to their toxicity and the acquired resistance by cancer cells. Therefore, synthetic retinoids were developed, such as the atypical adamantyl reti...

Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Her...

Cancer Stem Cells (CSCs) are a sub-population of cells, identified in most tumors, responsible for the initiation, recurrence, metastatic potential, and resistance of different malignancies. In prostate cancer (PCa), CSCs were identified and thought to be responsible for the generation of the lethal subtype, commonly known as Castration-Resistant P...

Immunophenotyping of spheres derived from human and murine prostate cancer cell lines. Immunofluorescent images of PC3, DU145, 22RV1, RWPE-1, PLum-AI, PLum-AD derived prostatospheres, stained for selected cancer stem cell markers including CD44, SOX2, CD117, and CD49f (white arrows). Those cancer stem cell markers have been shown to identify putati...

List of Human and Mouse primers for real-time PCR.

Recorded growth of prostatospheres in Matrigel™ matrix. This high-resolution movie shows the growth of single cell suspensions of wt murine prostate into individual spheres. This technique overcomes the limitations of culturing prostate spheroids in suspension, by limiting the migration and aggregation of generated spheres. This time-lapse movie of...

Relative mRNA expression of cancer stem cell markers in prostatospheres. The relative mRNA expression of CD44, CD133, SSEA4, c-Kit, NKx3.1, and OCT-4 in prostatospheres derived from human-derived prostate cancer cell lines (PC3, DU45, RWPE1, and 22RV1), and the relative mRNA expression of CD49f and CD24 in prostatospheres derived from murine prosta...

[This corrects the article DOI: 10.18632/oncotarget.1994.].

Metastatic progression in patients with prostate cancer is common despite pharmacologic inhibition of androgen receptor signaling. This drug resistance is associated with increased signaling through the transforming growth factor-β (TGF-β) signaling pathway. We found the type I/II/IV collagen-binding protein transforming growth factor-β (TGF-β)-ind...

Background: ETS variant gene 6 (ETV6) is a putative tumor suppressor and repressed by epidermal growth factor receptor (EGFR) signaling in prostate cancer. Since EGFR antagonists seem ineffective in castration-resistant prostate cancer (CRPC), we aim to study the role of ETV6 in the development of drug resistance. Methods: Etv6 target gene was v...

Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen–binding protein transforming growth factor–β (TGFβ)–induced protein (TGFBI) as...

ETV6 is an ETS transcription factor and a putative tumor suppressor in prostate cancer according to several genomic analyses. However, its cellular functions and upstream regulating signaling remain unclear. We demonstrated that ETV6 suppresses the prostate cancer progression and that ETV6 levels are negatively associated with advanced prostate can...

It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulati...

Gastric cancer is the second most common cause of cancer mortality worldwide. Most gastric cancer patients are asymptomatic until the advanced stages, for which current therapeutic treatments are suboptimal. 5-Fluorouracil (5-FU), an antimetabolite agent, is widely used in gastric cancer therapy. However, the presence of drug resistance in gastric...

Dysregulation of the epidermal growth factor receptor (EGFR) signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential...

Bone metastasis is the hallmark of progressive and castration resistant prostate cancers. miR-1 levels are decreased in clinical samples of primary prostate cancer and further reduced in metastases. SRC has been implicated as a critical factor in bone metastasis, and here we show that SRC is a direct target of miR-1. In prostate cancer patient samp...

Aberrant activation of Ras and WNT signaling are key events that have been shown to be up-regulated in prostate cancer that has metastasized to the bone. However, the regulatory mechanism of combinatorial Ras and WNT signaling in advanced prostate cancer is still unclear. TCF7, a WNT signaling-related gene, has been implicated as a critical factor...

A tumor suppressor role for miR-203 in RAS-dependent prostate cancer metastasis has been described recently by our group. We have explored the regulatory mechanisms by which miR-203 is being regulated through EGFR signaling. We investigated the molecular mechanism of metastasis and identified novel roles of genes that interact with miR-203 downstre...

The SRC kinase has pivotal roles in multiple developmental processes and in tumor progression. An inverse relationship has been observed between androgen receptor (AR) activity and SRC signaling in advanced prostate cancer (PCa); however, the modulation of AR/SRC crosstalk that leads to metastatic PCa is unclear. Here, we showed that patients with...

Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in t...

The recurrence of prostate cancer metastases to bone after androgen deprivation therapy is a major clinical challenge. We identified FN14 (TNFRSF12A), a TNF receptor family member, as a factor that promotes prostate cancer bone metastasis. In experimental models, depletion of FN14 inhibited bone metastasis, and FN14 could be functionally reconstitu...

Activation of EGFR signaling pathway leads to prostate cancer bone metastasis; however, therapies targeting EGFR have demonstrated limited effectiveness and led to drug resistance. miR-203 levels are down-regulated in clinical samples of primary prostate cancer and further reduced in metastatic prostate cancer. Here we show that ectopic miR-203 exp...

Epithelial-mesenchymal transition (EMT) is implicated in various pathological processes within the prostate, including benign prostate hyperplasia (BPH) and prostate cancer progression. However, an ordered sequence of signaling events initiating carcinoma-associated EMT has not been established. In a model of transforming growth factor β (TGFβ)-ind...

The tumorigenic origin of Synaptophysin+ cells in Plum-C orthotopic tumors. A representative section of Plum-C orthotopic tumors co-stained for Synaptophysin, P-AKT, and Dapi. Scale bar = 10 µm. (TIF)

Pten-/-TP53-/- cell lines form adenocarcinoma in vivo and express various differentiation markers. (A) Subcutaneous tumor was generated by injecting male nu/nu mice with PLum-P and PLum-C cells. Cross sections of subcutaneous tumors stained with H&E showing typical adenocarcinoma generated by PLum-P (left panel) and PLum-C (right panel) cells are s...

Prostate cancers of luminal adenocarcinoma histology display a range of clinical behaviors. Although most prostate cancers are slow-growing and indolent, a proportion is aggressive, developing metastasis and resistance to androgen deprivation treatment. One hypothesis is that a portion of aggressive cancers initiate from stem-like, androgen-indepen...

Loss of PTEN and loss of TP53 are common genetic aberrations occurring in prostate cancer. PTEN and TP53 contribute to the regulation of self-renewal and differentiation in prostate progenitors, presumptive tumor initiating cells for prostate cancer. Here we characterize the transformed phenotypes resulting from deletion of the Pten and TP53 tumor...