Hui-Wen Lo Laboratory
My research interests are primarily in molecular and cell
biology that underlies tumor growth, tumor progression and response to cancer
therapy. We have been focused on two cancer types, namely, breast cancer and
glioblastoma, the most common and deadliest brain malignancy in adults. More
recently, we are exploring prostate cancer biology and experimental
Aberrant cell signaling is a major hallmark of almost all types of cancer.
Thus, the majority of targeted therapies have been directed against tyrosine
and Ser/Thr kinases that mediate cancer cell signaling pathways. In this
regard, my laboratory has been investigating several of these pathways,
including those mediated by EGFR and HER2, as well as, the effectors downstream
of both kinases, such as STAT3 and Akt. Our work has led to the discovery of
several novel signaling axes within the EGFR/HER2 pathways and their
contributions to tumor cell growth, patient prognosis and resistance to
Another major direction of my laboratory is to investigate a novel
transcription factor within the sonic hedgehog pathway. We discovered the
existence of truncated glioma-associated oncogene homolog (tGLI1) in 2009 and
the evidence to date indicates that tGLI1 behaves as a gain-of-function GLI1
transcription factor that plays an important role in promoting tumor
progression and angiogenesis. Our results also suggest that tGLI1 may be
expressed in a tumor-specific fashion. Building on these observations, ongoing
projects in my laboratory aim at gaining a deeper understanding of tGLI1
functionality in human cancers and also the molecular events leading to tGLI1
synthesis in tumor cells.
Peer-Reviewed Publications (from 48)
1. Wang, S-C., Lien, H-C., Xia, W., Chen,
I-F., Lo, H.-W., Wang, Z., Ali-Seyed, M., Bartholomeusz, G., Ou-Yang,
F., Giri, D.K. and Hung, M.-C. Binding at and transactivation of COX-2 promoter
by nuclear tyrosine kinase receptor ErbB2. Cancer Cell 6:251-261, 2004.
H.-W., Hsu, S.-C.,
Ali-Seyed, M. Gunduz, M., Xia, W., Wei, Y., Bartholomeusz, G., Shih, J.-Y. and
Hung, M.-C. Nuclear interaction of EGFR and STAT3 in the activation of iNOS/NO pathway. Cancer Cell 6:575-589, 2005.
3. Lo, H.-W., Xia, W., Wei, Y., Ali-Seyed, M., Huang, S.-F. and Hung, M.-C. Novel prognostic value of nuclear
EGF receptor in breast cancer. Cancer Research 65:338-348, 2005.
H.-W., Day, C.-P., Hung, M.-C. Cancer-specific Gene Therapy. Advances in
Genetics 54:235-255, 2005.
Hanada, N., Lo, H.-W. (co-first author), Day, C.-P.,
Pan, Y., Nakajima, Y. and Hung, M-C. Co-regulation of
B-Myb expression by E2F1 and EGF receptor. Molecular Carcinogenesis 45:10-17, 2006.
H.-W. and Hung, M.-C.
Nuclear EGFR signaling network in
cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway
and patient survival. British Journal of Cancer 94:184-188, 2006.
7. Lo, H.-W., Ali-Seyed M.,
Wu, Y., Bartholomeusz, G., Hsu, Sheng-Chieh, and Hung, M.-C.
Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin b1
and CRM1. Journal of Cellular Biochemistry 98:1570-1583, 2006.
H.-W., Hsu, S.-C.,
and Hung, M.-C. EGFR signaling pathway in breast
cancers: from traditional signal transduction to direct nuclear
translocalization. Breast Cancer Research and
Treatment 95:211-218, 2006.
H.-W., Hsu, S-C., Xia, W., Cao, X., Shih, J.-Y.,
Wei, Y., Abbruzzese, J. L., Hortobagyi, G. N. and
Hung, M.-C. Epidermal growth factor receptor cooperates with signal
transducer and activator of transcription 3 to induce epithelial-mesenchymal
transition in cancer cells via up-regulation of TWIST gene expression. Cancer
Research 67:9066-9076, 2007.
10. Lo, H.-W. (corresponding author), et
activated STAT3 frequently co-expresses with EGFR in high-grade gliomas and
targeting STAT3 sensitizes them to Iressa and alkylators. Clinical Cancer
Research 14:6042-6054, 2008.
11. Lo, H.-W. (corresponding author), et
al. A novel splice variant of GLI1 that promotes glioblastoma cell migration
and invasion. Cancer Research 17:6790-6798, 2009.
therapy in malignant glioma: Novel aspects and mechanisms of drug resistance. (invited review) Current Molecular Pharmacology
H.-W. (corresponding author), et al. COX-2
is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3
signaling axes. (Selected as Journal Highlight; the most cited article
published in 2010 in Molecular Cancer Research) Molecular Cancer Research
14. Zhu, H., Cao, X., Ali-Osman, F., Keir, S. and Lo, H.-W. EGFR and EGFRvIII interact with PUMA
to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis
independent of EGFR kinase activity. Cancer Letters 294:101-110, 2010.
H. and Lo, H.-W. The human
glioma-associated oncogene Homolog 1 (GLI1) family of transcription factors in
gene regulation and diseases. (invited review) Current Genomics 11:238-245,
16. Lo, H.-W. Nuclear Mode of
the EGFR Signaling Network: Biology, Prognostic Value, and Therapeutic
Implications. (invited review) Discovery Medicine 10:44-51, 2010.
17. Lo, H.-W. Emerging
therapeutic targets and agents for glioblastoma therapy. (invited editorial)
Anti-Cancer Agents in Medicinal Chemistry Part I. 10(6):437, 2010 and Part II.
18. Lo, H.-W. Targeting
Ras-RAF-ERK and its interactive pathways as a novel therapy for malignant
gliomas. (invited review) Current Cancer Drug Targets 10:840-848, 2010.
19. Lo, H.-W. EGFR-targeted
Cancer Therapy: Promise, Problems and Potential Solutions. Translational
Medicine 1:105e. doi:10.4172/2161-1025.1000105e, 2011.
X., Zhu, H., Ali-Osman, F. and Lo, H.-W.
EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced
mitochondrial translocalization: A novel mechanism of EGFR-driven antagonism of
apoptosis. Molecular Cancer 10:26, 2011.
P., Xing, F., Huang, X., Zhu, H., Lo,
H.-W., Zhong, X., Pruitt, S. and Robertson, C. HIFU as a Neoadjuvant
Therapy in Cancer Treatment. 10TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC
ULTRASOUND (ISTU 2010) 1359:289-294, 2011.
22. Cao, X., Geradts, J., Dewhirst, M. and Lo, H.-W. Upregulation of VEGF-A and
CD24 gene expression by the tGLI1 transcription factor contributes to the
aggressive behavior of breast cancer cells. Oncogene 31:104-115, 2012.
RL. and Lo, H.-W. Hedgehog Pathway
and GLI1 Isoforms in Human Cancer. (invited review) Discovery Medicine
W. and Lo, H.-W. Landscape of EGFR
Signaling Network in Human Cancers: Biology and Therapeutic Response in
Relation to Receptor Subcellular Locations. (invited review) Cancer Letters
X., Yuan, F., Liang, M., Lo*, H.-W. (co-corresponding
author), Shinohara*, M.
L., Robertson, C., Zhong*, P. M-HIFU inhibits tumor growth via suppressing
STAT3 activity and enhancing tumor specific immunity in a transplant tumor
model of prostate cancer. PLoS ONE 7: e41632, 2012. *Co-corresponding Authors
R. L. and Lo, H.-W. Identification,
Functional Characterization and Pathobiological Significance of GLI1 Isoforms
in Human Cancers. In Vitamins & Hormones-HEDGEHOG SIGNALING. Ed: Gerald
Litwack. Elsevier Inc., Volume 88, pp. 115-140, 2012.
RL. and Lo, H.-W. Dacomitinib, an
Emerging HER-Targeted Therapy for Non-Small Cell Lung Cancer. Journal of
Thoracic Disease, 4:639-642, 2012.
28. Lo, H.-W. Akt destabilizes
p57Kip2: Akt at the converging crossroad? (Invited News & Views) Cell Cycle
29. Han, W., Carpenter, RL, and
Lo, H.-W. TGLI1 upregulates
expression of VEGFR2 and VEGF-A, leading to a robust VEGF-VEGFR2 autocrine loop
and cancer cell growth. doi:10.1166/ch.2013.1006. Cancer Hallmarks 1: 28-37,
R. L and Lo, H.-W. Regulation of
Apoptosis by HER2 in Breast Cancer. Journal of Carcinogenesis & Mutagenesis
R. L, Han, W., Paw, I. and Lo, H.-W. HER2
phosphorylates and destabilizes proapoptotic PUMA, leading to antagonized
apoptosis in cancer cells. PLoS ONE 8(11):e78836, 2013.
W., Carpenter, R. L., Cao, X. and Lo,
H.-W. STAT1 gene expression is enhanced by nuclear EGFR and HER2 via
cooperation with STAT3. Molecular Carcinogenesis 52(12):959-969, 2013.
H., Carpenter, R. L, Han, W., and Lo,
H.-W. The GLI1 splice variant TGLI1 is a novel mediator of glioblastoma
angiogenesis and growth. Cancer Letters 343(1):51-61. 2014.
R. L. and Lo, H.-W. STAT3-regulated
Genes Relevant to Human Cancers. In Special Issue: STAT3 Signalling in Cancer:
Friend or Foe. Cancers 6:897-925, 2014.
R. L., Paw, I, Dewhirst, M. W., Lo,
H.-W. Akt phosphorylates and activates HSF-1 independent of heat shock,
leading to Slug overexpression and epithelial-mesenchymal transition (EMT) of
HER2-overexpressing breast cancer cells. Oncogene, Published ahead of print,
Jan 27, 2014. PMC4112182, 2014