Kwok-Ming Yao

Kwok-Ming Yao
The University of Hong Kong | HKU · Li Ka Shing Faculty of Medicine

BSc, PhD
Serving as Principal Lecturer at the Sch of Biomed Sc from 2021-

About

78
Publications
8,225
Reads
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3,776
Citations
Introduction
Kwok-Ming Yao currently works at the School of Biomed. Sci., LKS Fac. of Med., The University of Hong Kong. Kwok-Ming does research in Cell Biology, Developmental Biology and Endocrinology. Ongoing projects: FOXM1 and regulation of cell proliferation and survival of cancer and stem cells. PDZD2/sPDZD2 and regulation of Hedgehog (Hh) signaling.
Additional affiliations
December 1996 - present
The University of Hong Kong
Position
  • Professor (Associate)
June 1992 - December 1993
Harvard Medical School
Position
  • PostDoc Position

Publications

Publications (78)
Article
Full-text available
Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative disea...
Article
Full-text available
Secreted PDZD2 (sPDZD2) is a signaling molecule generated upon proteolytic processing of the multi-PDZ-containing protein PDZD2. Previous analysis of gene-trap mice deficient in the synthesis of full-length PDZD2, but not the secreted form, revealed a role of PDZD2 in the regulation of glucose-stimulated insulin secretion. Here, using the pancreati...
Article
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One hallmark of cancer cells is sustaining proliferative signaling that leads to uncontrolled cell proliferation. Both the Forkhead box (FOX) M1 transcription factor and the Epidermal Growth Factor (EGF) receptor Pathway Substrate 8 (EPS8) are known to be activated by mitogenic signaling and their levels upregulated in cancer. Well-known to regulat...
Data
Immunoprecipitation assay using C33A cells. Lysates prepared from another cervical cancer cell line C33A were subjected to IP with anti-FOXM1 antibody and control antibody (rabbit anti-ETS2). Immunoblot analysis using anti-EPS8 antibody indicated that endogenous EPS8 was pulled down.
Article
Effective retinal drug delivery remains a challenge for treating vision-threatening diseases. Encapsulated-cell therapy (ECT) can provide local drug delivery without repeated invasive injections but is plagued by unsteady performance and biosafety issues. Here, an injectable composite alginate-collagen (CAC) ECT gel with a Tet-on inducible pro-casp...
Article
Full-text available
A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transient...
Article
Full-text available
Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting...
Article
Full-text available
Human embryonic stem cells (hESCs) exhibit unique cell cycle structure, self-renewal and pluripotency. The Forkhead box transcription factor M1 (FOXM1) is critically required for the maintenance of pluripotency in mouse embryonic stem cells and mouse embryonal carcinoma cells, but its role in hESCs remains unclear. Here, we show that FOXM1 expressi...
Article
Tumorigenesis arises very often from dysregulated cell proliferation mechanisms. The Forkhead box transcription factor FOXM1 is a critical regulator of cell cycle progression as it affects the expression of genes that control the cell cycle, such as cyclin B1, cdc25B, etc. It is upregulated in various cancers, including cervical cancer. In a yeast...
Article
Full-text available
Transforming growth factor (TGF)-β-activating kinase 1 (TAK1) is a serine/threonine kinase which is frequently associated with human cancer progression. However, its functional role in tumorigenesis is still controversial. Here, we report that TAK1 enhances the oncogenic capacity of ovarian cancer cells through the activation of NF-κB signaling. We...
Article
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AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remai...
Article
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Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic...
Article
Full-text available
The forkhead box (FOX) M1 transcription factor is required to maintain the proliferation of cancer cells. Two transcriptionally active isoforms of FOXM1, FOXM1b and FOXM1c, have been identified, but their functional differences remain unclear. FOXM1c is distinguished from FOXM1b by an extra exon (exon Va) that contains an ERK1/2 target sequence. Ba...
Article
  Our laboratory has recently demonstrated a melatonin MT(1) receptor-mediated antiproliferative signaling mechanism in androgen receptor (AR)-positive prostate epithelial cells which involves up-regulation of p27(Kip1) through dual activation of Gα(s) /protein kinase A (PKA) and Gα(q) /protein kinase C (PKC) in parallel, and down-regulation of act...
Article
Full-text available
Background: The phosphoinositide 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently aberrantly activated in ovarian cancer and confers the chemoresistant phenotype of ovarian cancer cells. LY294002 (PI3K inhibitor) and metformin (5¶-adenosine monophosphate [AMP]-activated pro...
Article
Aberrant activation of Hedgehog (Hh) signalling has been implicated in the pathogenesis of human cancers. However, the cognate molecular mechanisms contributing to this disregulated pathway are incompletely understood. In this study, we showed that Zic2 was frequently over-expressed and associated with high-grade cervical cancer (p = 0.032), high l...
Article
The phosphoinositide 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently aberrantly activated in ovarian cancer and confers the chemoresistant phenotype of ovarian cancer cells. LY294002 (PI3K inhibitor) and metformin (5'-adenosine monophosphate [AMP]-activated protein kinase...
Article
Full-text available
The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a correspondin...
Data
XTT assay showed that no significant change in the cell proliferation rate of OVCA433 by treatment of thiostrepton in a lower dose (5 and 10 µM) within 3 days. (TIF)
Data
(Upper) Western blot analysis showed that no change in FOXM1 expression in SKOV3 upon treatment of 10 µM U0126 for 4 to 8 Hrs. (Lower) Wound healing assay demonstrated that no change in cell migration of SKOV3 upon treatment with 10 µM U0126 for 12–24 hrs when compared to untreated control. (TIF)
Data
Wound healing assay showed no influence in cell migration of SKOV3 upon treatment with 5 µM and 10 µM of thiostrepton for 12–24 hrs when compared to untreated control. (TIF)
Article
Full-text available
Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metast...
Article
Full-text available
Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-cell development and function. A Cre-LoxP...
Article
Melatonin has been shown to inhibit the proliferation of malignant and transformed human prostate epithelial cells by transcriptional up-regulation of p27(Kip1) expression via MTNR1A receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel. Given that melatonin MTNR1A receptor is a G protein-coupled receptor, th...
Article
The proliferation-associated transcription factor FOXM1 is essential for cell cycle progression into mitosis. Using synchronized human fibroblasts we detected, by immunostaining, that FOXM1 is localized predominantly in the cytoplasm in cells at late-G1 and S phases. Nuclear translocation occurs just before progression into the G2/M phase of the ce...
Article
Expression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet beta cells, but not in exocrine or alpha cells, suggesting a role for Pdzd2 in the regulation of pancreatic beta-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were v...
Article
Full-text available
We recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate m...
Article
Full-text available
Loss of growth inhibitory response to transforming growth factor-beta (TGF-beta) is a common feature of epithelial cancers. Recent studies have reported that genetic lesions and overexpression of oncoproteins in TGF-beta/Smads signalling cascade contribute to the TGF-beta resistance. Here, we showed that the overexpressed FOXG1 was involved in atte...
Article
Full-text available
The voltage-gated sodium channel Na(V)1.8 is expressed exclusively in nociceptive sensory neurons and plays an important role in pain pathways. Na(V)1.8 cannot be functionally expressed in non-neuronal cells even in the presence of beta-subunits. We have previously identified Pdzd2, a multi PDZ-domain protein, as a potential interactor for Na(V)1.8...
Article
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PDZ domains are versatile protein interaction modules with the ability to dimerize and to recognize internal and carboxy-terminal peptide motifs. Their function in mediating the formation of multi-molecular signaling complexes is best understood at neuronal and epithelial membranes. In a screen for interactors that regulate transcription factor fun...
Article
Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-t...
Article
Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT(1) and MT(2) rece...
Article
Full-text available
The RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) pathway plays a pivotal role in various cellular responses, including cellular growth, differentiation, survival and motility. Constitutive activation of the ERK pathway has been linked to the development and progression of human cancers. Here, we reported that mitogen-activated protein ki...
Article
The Forkhead Box M1 (FOXM1) transcription factor plays a crucial role in regulating expression of cell cycle genes which are essentially involved in cell proliferation, differentiation and transformation. Recent studies have reported that aberrant expression of FOXM1 in a variety of human cancers is associated with their aggressive behaviour. Howev...
Article
Full-text available
The Forkhead box transcription factor FoxM1 is expressed in proliferating cells. When it was depleted in mice and cell lines, cell cycle defects and chromosomal instability resulted. Premature senescence was observed in embryonic fibroblasts derived from FoxM1 knock-out mice, but the underlying cause has remained unclear. To investigate whether Fox...
Article
Early-trimester human fetal pancreas is a promising potential source of pancreatic progenitor cells. However, the ethical controversy associated with the source of these cells, and technical difficulties associated with their differentiation into insulin-producing cells have limited both their availability and utility. This study aimed to character...
Article
Mammalian cell culture technology has been used for decades in mass production of therapeutic proteins. However, unrestricted cell proliferation usually results in low-protein productivity. Controlled proliferation technologies such as metabolism intervention and genetic manipulation are therefore applied to enhance the productivity. Nevertheless,...
Conference Paper
Full-text available
Introduction: PDZD2 (PDZ-domain-containing 2), a multi-PDZ-domain protein, is found to selectively express in cells of pancreatic islet and it was shown to localize to the nucleus as well as the ER. As PDZD2 is identified to carry a functional NLS, it is suggested to interact with E2A proteins in regulating the gene expression of insulin and other...
Article
There is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone-refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT(1) receptor expression in pros...
Article
Full-text available
A possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and...
Article
Full-text available
In this study, we have identified the Forkhead transcription factor FoxM1 as a physiological regulator of estrogen receptor alpha (ERalpha) expression in breast carcinoma cells. Our survey of a panel of 16 different breast cell lines showed a good correlation (13/16) between FoxM1 expression and expression of ERalpha at both protein and mRNA levels...
Article
PDZD2 (PDZ domain containing 2) is a multi-PDZ protein expressed in pancreas and many other tissues. PDZD2 shows extensive homology to pro-interleukin-16 (pro-IL-16) and is localized mainly to the endoplasmic reticulum. We have recently demonstrated that PDZD2, like pro-IL-16, is proteolytically cleaved at its C-terminus to generate a secreted prot...
Article
Full-text available
Transcriptional coactivators are essential mediators of signal amplification in the regulation of gene expression in response to hormones and extracellular signals. We previously identified Bridge-1 (PSMD9) as a PDZ-domain coregulator that augments insulin gene transcription via interactions with the basic helix-loop-helix transcription factors E12...
Article
Well-orchestrated transcriptional regulation of pancreatic beta cells is essential for insulin production and glucose homeostasis. Pancreas duodenum homeobox-1 (PDX-1) is a key regulator of glucose-dependent insulin production and glucose metabolism. We find that PDX-1 interacts with the PDZ-domain coactivator Bridge-1 in yeast interaction trap ass...
Article
Full-text available
We have previously shown that the expression of SmCP which encodes Solanum melongena cysteine proteinase is ethylene-inducible and is under circadian control. To understand the regulation of SmCP, a 1.34-kb SmCP 5′-flanking region and its deletion derivatives were analyzed for cis-elements using GUS and luc fusions and by in vitro binding assays. A...
Article
Full-text available
The forkhead box (FOX) transcription factor FOXM1 is ubiquitously expressed in proliferating cells. FOXM1 expression peaks at the G2/M phase of the cell cycle and its functional deficiency in mice leads to defects in mitosis. To investigate the role of FOXM1 in the cell cycle, we used synchronized hTERT-BJ1 fibroblasts to examine the cell cycle-dep...
Article
Full-text available
VCY2 is a testis-specific protein that locates in a frequently deleted azoospermia factor c region on chromosome Yq. Although its genomic structure has been characterized, the function of VCY2 is still unknown. To gain insight regarding the likely function of VCY2, we investigated the proteins that interact with VCY2 using the yeast two-hybrid syst...
Article
Full-text available
PDZD2 (PDZ-domain-containing 2; also known as PAPIN, AIPC and PIN1) is a ubiquitously expressed multi-PDZ-domain protein. We have shown that PDZD2, which shows extensive homology to pro-interleukin-16 (pro-IL-16), is localized mainly to the endoplasmic reticulum (ER). Pro-IL-16 is cleaved in a caspase-3-dependent mechanism to generate the secreted...
Article
Full-text available
We have previously shown that SmCP, the gene encoding Solanum melongena cysteine proteinase, is expressed during developmental events associated with programmed cell death (PCD) suggesting its involvement in protein degradation during these events (Xu and Chye, Plant Journal 17 (1999) 321-327). Here, we investigated the regulation of SmCP expressio...
Article
VCY2 locates in the AZFc region on chromosome Yq and is frequently deleted in infertile men with severe oligozoospermia or azoospermia. VCY2 is a testis-specific protein with unknown function. This study was to identify the protein that interacts with VCY2. We used the full-length VCY2 as bait to screen the human testis cDNA library using yeast two...
Article
FoxM1 (previously named WIN, HFH-11 or Trident) is a Forkhead box (Fox) transcription factor widely expressed in proliferating cells. Various findings, including a recent analysis of FoxM1 knockout mice, suggest that FoxM1 is required for normal S-M coupling during cell cycle progression. To study the regulatory role of FoxM1 and its downstream reg...
Article
Melatonin inhibited thymidine incorporation into human choriocarcinoma JEG-3 cells at physiological and pharmacological concentrations in the present study. Gene expression of MT2 receptor, but not that of mt1 receptor, was detected in JEG-3 cells by reverse transcription-polymerase chain reaction (RT-PCR). The gene expression profile of the two hu...
Article
Full-text available
Proteins in the E2A family of basic helix-loop-helix transcription factors are important in a wide spectrum of physiologic processes as diverse as neurogenesis, myogenesis, lymphopoeisis, and sex determination. In the pancreatic beta cell, E2A proteins, in combination with tissue-specific transcription factors, regulate expression of the insulin ge...