Kyung-min Lee
@utsouthwestern
UT SOUTHWESTERN MEDICAL CENTER
EDUCATION
BS Hanyang University
PhD Hanyang University
RESEARCH INTERESTS
Cancer, Metabolism, Drug resistance
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Kyung-min Lee, Angel L. Guerrero-Zotano, Alberto Servetto, Dhivya R. Sudhan, Chang-Ching Lin, Luigi Formisano, Valerie M. Jansen, Paula González-Ericsson, Melinda E. Sanders, Thomas P. Stricker,et al.
Springer Science and Business Media LLC
Abstract The 17q23 amplicon is associated with poor outcome in ER+ breast cancers, but the causal genes to endocrine resistance in this amplicon are unclear. Here, we interrogate transcriptome data from primary breast tumors and find that among genes in 17q23, PRR11 is a key gene associated with a poor response to therapeutic estrogen suppression. PRR11 promotes estrogen-independent proliferation and confers endocrine resistance in ER+ breast cancers. Mechanistically, the proline-rich motif-mediated interaction of PRR11 with the p85α regulatory subunit of PI3K suppresses p85 homodimerization, thus enhancing insulin-stimulated binding of p110-p85α heterodimers to IRS1 and activation of PI3K. PRR11-amplified breast cancer cells rely on PIK3CA and are highly sensitive to PI3K inhibitors, suggesting that PRR11 amplification confers PI3K dependence. Finally, genetic and pharmacological inhibition of PI3K suppresses PRR11-mediated, estrogen-independent growth. These data suggest ER+/PRR11-amplified breast cancers as a novel subgroup of tumors that may benefit from treatment with PI3K inhibitors and antiestrogens.
Kyungmin Lee, Sang-Hyun Lee, Wooil Kim, Jangwook Lee, Jong-Gil Park, Jang-Seong Kim, Jung Tae Kim, Yea Eun Kang, Minho Shong, Hyo Jin Lee,et al.
Bioscientifica
Anaplastic thyroid cancer (ATC) is a rapidly growing, highly metastatic cancer with limited therapeutic alternatives, thus targeted therapies need to be developed. This study aimed to examine desmoglein 2 (Dsg2) expression in ATC and its biological role and potential as a therapeutic target in ATC. Consequently, Dsg2 was downregulated or aberrantly expressed in ATC tissues. ATC patients with low Dsg2 expression levels also presented with distant metastasis. Dsg2 depletion significantly increased cell migration and invasion, with a relatively limited effect on ATC cell proliferation in vitro and increased distant metastasis in vivo. Dsg2 knockdown induced cell motility through the hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1 signaling axis, with no alterations in the expression of EMT-related molecules. Further, specific targeting of c-Met significantly inhibited the motility of shDsg2-depleted ATC cells. Decreased membrane Dsg2 expression increased the metastatic potential of ATC cells. These results indicate that Dsg2 plays an important role in ATC cell migration and invasiveness. Therapies targeting c-Met might be effective among ATC patients with low membrane Dsg2 expression levels, indicating that the analysis of Dsg2 expression potentially provides novel insights into treatment strategies for ATC.
Seung-Nam Jung, Yea Eun Kang, Gun Ho Lee, Lihua Liu, Chan Oh, Yan Li Jin, Mi Ae Lim, Kyungmin Lee, Taejeong Oh, Ho-Ryun Won,et al.
The Endocrine Society
Abstract Background Brn3a/Pou4f1 is a class IV POU domain-containing transcription factor and has been found to be expressed in a variety of cancers. However, the mechanism and action of Brn3a in thyroid cancer has not been investigated. Purpose To investigate the role of Brn3a in thyroid cancer progression and its clinical implication. Methods We examined Brn3a expression status in patients with thyroid cancer and analyzed relationships between Brn3a expression and clinicopathological findings using The Cancer Genome Atlas (TCGA) database. For functional in vitro analysis, proliferation, migration, invasion assay, and Western blotting were performed after overexpression or suppression of Brn3a. Results The promoter hypermethylation of Brn3a was found in patients with aggressive thyroid cancer and Brn3a was downregulated in tissues of patients with thyroid cancer. In TCGA database, the low-Brn3a-expression group revealed a more aggressive phenotype, including T stage and extrathyroid extension when compared with the high-Brn3a-expression group. Overexpression of Brn3a suppressed cell migration and invasion via regulation of epithelial-mesenchymal transition (EMT)-associated proteins in thyroid cancer cell lines. Brn3a overexpression also downregulated signal transducer and activator of transcription 3 (STAT3) signaling through suppression of tyrosine-protein kinase Met (c-MET). In contrast, knockdown of Brn3a by small interfering ribonucleic acid (siRNA) significantly increased cell migration and invasion through upregulation of c-MET/STAT3. These results imply that Brn3a suppresses tumor metastasis via c-MET/STAT3 inhibition and EMT suppression in thyroid cancer. Conclusions Our findings show that Brn3a is a potential tumor suppressor that leads to reduced cancer cell migration and invasion in thyroid cancer. Elucidation of the Brn3a-regulated cancer pathways may therefore provide novel therapeutic strategies to control thyroid cancer metastasis.
Kyungmin Lee, Jae Won Chang, Chan Oh, Lihua Liu, Seung-Nam Jung, Ho-Ryun Won, Young Il Kim, Ki-Sang Rha, and Bon Seok Koo
Elsevier BV
Dhivya R. Sudhan, Angel Guerrero-Zotano, Helen Won, Paula González Ericsson, Alberto Servetto, Mariela Huerta-Rosario, Dan Ye, Kyung-min Lee, Luigi Formisano, Yan Guo,et al.
Elsevier BV
Dhivya R. Sudhan, Angel Guerrero-Zotano, Helen Won, Paula González Ericsson, Alberto Servetto, Mariela Huerta-Rosario, Dan Ye, Kyung-min Lee, Luigi Formisano, Yan Guo,et al.
Elsevier BV
Hitisha K. Patel, Nianjun Tao, Kyung-Min Lee, Mariela Huerta, Heike Arlt, Tara Mullarkey, Steven Troy, Carlos L. Arteaga, and Teeru Bihani
Springer Science and Business Media LLC
Abstract Background Addition of CDK4/6 inhibitors (CDK4/6i) to endocrine therapy significantly increased progression-free survival, leading to their approval and incorporation into the metastatic breast cancer treatment paradigm. With these inhibitors being routinely used for patients with advanced estrogen receptor-positive (ER+) breast cancer, resistance to these agents and its impact on subsequent therapy needs to be understood. Considering the central role of ER in driving the growth of ER+ breast cancers, and thus endocrine agents being a mainstay in the treatment paradigm, the effects of prior CDK4/6i exposure on ER signaling and the relevance of ER-targeted therapy are important to investigate. The objective of this study was to evaluate the anti-tumor activity of elacestrant, a novel oral selective estrogen receptor degrader (SERD), in preclinical models of CDK4/6i resistance. Methods Elacestrant was evaluated as a single agent, and in combination with alpelisib or everolimus, in multiple in vitro models and patient-derived xenografts that represent acquired and “de novo” CDK4/6i resistance. Results Elacestrant demonstrated growth inhibition in cells resistant to all three approved CDK4/6i (palbociclib, abemaciclib, ribociclib) in both ESR1 wild-type and mutant backgrounds. Furthermore, we demonstrated that elacestrant, as a single agent and in combination, inhibited growth of patient-derived xenografts that have been derived from a patient previously treated with a CDK4/6i or exhibit de novo resistance to CDK4/6i. While the resistant lines demonstrate distinct alterations in cell cycle modulators, this did not affect elacestrant’s anti-tumor activity. In fact, we observe that elacestrant downregulates several key cell cycle players and halts cell cycle progression in vitro and in vivo. Conclusions We demonstrate that breast cancer tumor cells continue to rely on ER signaling to drive tumor growth despite exposure to CDK4/6i inhibitors. Importantly, elacestrant can inhibit this ER-dependent growth despite previously reported mechanisms of CDK4/6i resistance observed such as Rb loss, CDK6 overexpression, upregulated cyclinE1 and E2F1, among others. These data provide a scientific rationale for the evaluation of elacestrant in a post-CDK4/6i patient population. Additionally, elacestrant may also serve as an endocrine backbone for rational combinations to combat resistance.
Luigi Formisano, Yao Lu, Alberto Servetto, Ariella B. Hanker, Valerie M. Jansen, Joshua A. Bauer, Dhivya R. Sudhan, Angel L. Guerrero-Zotano, Sarah Croessmann, Yan Guo,et al.
Springer Science and Business Media LLC
Yea Eun Kang, Jung Tae Kim, Mi Ae Lim, Chan Oh, Lihua Liu, Seung-Nam Jung, Ho-Ryun Won, Kyungmin Lee, Jae Won Chang, Hyon-Seung Yi,et al.
MDPI AG
Fibroblast growth factor 21 (FGF21) plays important roles in regulating glucose, lipid, and energy metabolism; however, its effects in tumors remain poorly understood. To understand the role of FGF21 in regulating tumor aggressiveness in thyroid cancer, serum levels of FGF21 were measured in healthy subjects and patients with papillary thyroid cancer (PTC), and expression levels of FGF21, FGF receptors (FGFRs), and β-klotho (KLB) were investigated in human thyroid tissues. The cell viability, migrating cells, and invading cells were measured in PTC cells after treatment with recombinant FGF21. Higher serum levels of FGF21 were found in patients with thyroid cancer than in control participants, and were significantly associated with body mass index (BMI), fasting glucose levels, triglyceride levels, tumor stage, lymphovascular invasion, and recurrence. Serum FGF21 levels were positively correlated with the BMI in patients with PTC, and significantly associated with recurrence. Recombinant FGF21 led to tumor aggressiveness via activation of the FGFR signaling axis and epithelial-to-mesenchymal transition (EMT) signaling in PTC cells, and AZD4547, an FGFR tyrosine kinase inhibitor, attenuated the effects of FGF21. Hence, FGF21 may be a new biomarker for predicting tumor progression, and targeting FGFR may be a novel therapy for the treatment of obese patients with PTC.
Taekyu Lee, Plamen P. Christov, Subrata Shaw, James C. Tarr, Bin Zhao, Nagarathanam Veerasamy, Kyu Ok Jeon, Jonathan J. Mills, Zhiguo Bian, John L. Sensintaffar,et al.
American Chemical Society (ACS)
Kyung-min Lee, Keesoo Nam, Sunhwa Oh, Juyeon Lim, Young-Pil Kim, Jong Won Lee, Jong-Han Yu, Sei-Hyun Ahn, Sung-Bae Kim, Dong-Young Noh,et al.
Springer Science and Business Media LLC
Lihua Liu, Seung-Nam Jung, Chan Oh, Kyungmin Lee, Ho-Ryun Won, Jae Won Chang, Jin Man Kim, and Bon Seok Koo
Elsevier BV
Sarah Croessmann, Jonathan H. Sheehan, Kyung-min Lee, Gregory Sliwoski, Jie He, Rebecca Nagy, David Riddle, Ingrid A. Mayer, Justin M. Balko, Richard Lanman,et al.
American Association for Cancer Research (AACR)
Angel L. Guerrero-Zotano, Thomas P. Stricker, Luigi Formisano, Katherine E. Hutchinson, Daniel G. Stover, Kyung-Min Lee, Luis J. Schwarz, Jennifer M. Giltnane, Monica V. Estrada, Valerie M. Jansen,et al.
American Association for Cancer Research (AACR)
Kyungmin Lee, Jangwook Lee, Minjeong Kwak, Young-Lai Cho, Byungtae Hwang, Min Ji Cho, Na Geum Lee, Jongjin Park, Sang-Hyun Lee, Jong-Gil Park,et al.
Springer Science and Business Media LLC
Wooil Kim, Won Kon Kim, Kyungmin Lee, Min Jeong Son, Minjeong Kwak, Won Seok Chang, Jeong-Ki Min, Nam Woong Song, Jangwook Lee, and Kwang-Hee Bae
Informa UK Limited
Lihua Liu, Chan Oh, Jae Hyung Heo, Hee Sung Park, Kyungmin Lee, Jae Won Chang, Seung-Nam Jung, and Bon Seok Koo
Elsevier BV
Jongjin Park, Yeonsung Son, Na Geum Lee, Kyungmin Lee, Dong Gwang Lee, Jinhoi Song, Jaemin Lee, Seokho Kim, Min Ji Cho, Ju-Hong Jang,et al.
Elsevier BV
Angel L. Guerrero-Zotano, Thomas P. Stricker, Luigi Formisano, Katherine E. Hutchinson, Daniel G. Stover, Kyung-Min Lee, Luis J. Schwarz, Jennifer M. Giltnane, Monica V. Estrada, Valerie M. Jansen,et al.
American Association for Cancer Research (AACR)
Sarah Croessmann, Jonathan H. Sheehan, Kyung-min Lee, Gregory Sliwoski, Jie He, Rebecca Nagy, David Riddle, Ingrid A. Mayer, Justin M. Balko, Richard Lanman,et al.
American Association for Cancer Research (AACR)
Valerie M. Jansen, Neil E. Bhola, Joshua A. Bauer, Luigi Formisano, Kyung-Min Lee, Katherine E. Hutchinson, Agnieszka K. Witkiewicz, Preston D. Moore, Mónica Valéria Estrada, Violeta Sánchez,et al.
American Association for Cancer Research (AACR)
Kyung-min Lee, Jennifer M. Giltnane, Justin M. Balko, Luis J. Schwarz, Angel L. Guerrero-Zotano, Katherine E. Hutchinson, Mellissa J. Nixon, Mónica V. Estrada, Violeta Sánchez, Melinda E. Sanders,et al.
Elsevier BV
Valerie M. Jansen, Neil E. Bhola, Joshua A. Bauer, Luigi Formisano, Kyung-Min Lee, Katherine E. Hutchinson, Agnieszka K. Witkiewicz, Preston D. Moore, Mónica Valéria Estrada, Violeta Sánchez,et al.
American Association for Cancer Research (AACR)
Dong Hyun Jo, Kyungmin Lee, Jin Hyoung Kim, Hyoung Oh Jun, Younghoon Kim, Young-Lai Cho, Young Suk Yu, Jeong-Ki Min, and Jeong Hun Kim
Impact Journals, LLC
Yea Eun Kang, Jin-Man Kim, Koon Soon Kim, Joon Young Chang, Mingyu Jung, Junguee Lee, Shinae Yi, Hyeon Woo Kim, Jung Tae Kim, Kyungmin Lee,et al.
Impact Journals, LLC