PUBLICATIONS

SYNOPSIS

We are interested in understanding mechanisms of tumor progression and metastasis in gynecological cancers. Emphasis is on  consequences of contextual alterations in signaling due to stress, in order to identify therapeutic vulnerabilities and opportunities. Major methodologies used include: Animal models of ovarian cancer metastasis, cell line and patient derived primary cellular strategies, transcriptomics ( RNA seq), and proteomic approaches and pre- clinical exploration of therapeutic strategies ( antibody and small molecule)

Pubmed Link to Complete Bibliography ( Pubmed Index: Karthikeyan Mythreye)

Current Active Preprints/papers in review or revision:

Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition.  Mehri Monavarian,  Emily Faith Page,  Resha Rajkarnikar, Asha Kumari, Liz Quintero Macias,  Felipe Massicano, Nam Y Lee, Sarthak Sahoo,  Nadine Hempel, Mohit Kumar Jolly, Lara Ianov,  Elizabeth Worthey,  Abhyudai Singh, Eugenia V Broude,  Karthikeyan Mythreye . bioRxiv [Preprint]. 2023 Dec 6:2023.12.04.569970. doi: 10.1101/2023.12.04.569970. PMID: 38106208; PMCID: PMC10723298

Identification of Mfn2-S249 as a Phosphoregulatory Switch of Mitochondrial Fusion Dynamics
Sanjay Kumar, Aaron Ramonett, Tasmia Ahmed, Eun-A Kwak, Paola Cruz Flores, Hannah R. Ortiz, Paul R. Langlais, Karthikeyan Mythreye, Nam Y. Lee (in revisions). preprint: https://www.biorxiv.org/content/10.1101/2022.01.11.475884v1


PUBLISHED

2024

Activin levels correlate with lymphocytic infiltration in epithelial ovarian cancer. Evans ET, Page EF, Choi AS, Shonibare Z, Kahn AG, Arend RC, Mythreye K.  Cancer Med. 2024 Sep;13(17):e7368. doi: 10.1002/cam4.7368. PMID: 39248018; PMCID: PMC11381957. 

Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression. Javed Z, Shin DH, Pan W, White SR, Elhaw AT, Kim YS, Kamlapurkar S, Cheng YY, Benson JC, Abdelnaby AE, Phaëton R, Wang HG, Yang S, Sullivan MLG, St Croix CM, Watkins SC, Mullett SJ, Gelhaus SL, Lee N, Coffman LG, Aird KM, Trebak M, Mythreye K, Walter V, Hempel N. D EMBO Rep. 2024 Aug 27. doi: 10.1038/s44319-024-00232-4. Epub ahead of print. PMID: 39191946.

Targeted therapy in high grade serous ovarian Cancer: A literature review. Dinkins K, Barton W, Wheeler L, Smith HJ, Mythreye K, Arend RC.  Gynecol Oncol Rep. 2024 Jul 6;54:101450. doi: 10.1016/j.gore.2024.101450. PMID: 39092168; PMCID: PMC11292514.

Phosphoproteomic profiling identifies DNMT1 as a key substrate of beta IV spectrin-dependent ERK/MAPK signaling in suppressing angiogenesis.Flores PC, Ahmed T, Podgorski J, Ortiz HR, Langlais PR, Mythreye K, Lee NY.  Biochem Biophys Res Commun. 2024 Jun 4;711:149916. doi: 10.1016/j.bbrc.2024.149916. Epub 2024 Apr 10. PMID: 38613866; PMCID: PMC11089540.

Extracellular signals induce dynamic ER remodeling through αTAT1-dependent microtubule acetylation. Ortiz HR, Cruz Flores P, Podgorski J, Ramonett A, Ahmed T, Hempel N, Charest PG, Ellis NA, Langlais PR, Montfort WR, Mythreye K, Kumar S, Lee NY.  Neoplasia. 2024 Jul;53:101003. doi: 10.1016/j.neo.2024.101003. Epub 2024 May 16. PMID: 38759377; PMCID: PMC11127537.

Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-β signaling responses in ovarian cancer.Choi AS, Jenkins-Lane LM, Barton W, Kumari A, Lancaster C, Raulerson C, Ji H, Altomare D, Starr MD, Whitaker R, Phaeton R, Arend R, Shtutman M, Nixon AB, Hempel N, Lee NY, Mythreye K.  Cell Commun Signal. 2024 Feb 15;22(1):128. doi: 10.1186/s12964-024-01496-y. PMID: 38360757; PMCID: PMC10870443.

GPX3 supports ovarian cancer tumor progression in vivo and promotes expression of GDF15. Caroline Chang, Ya-Yun Cheng, Shriya Kamlapurkar, Sierra White, Priscilla W. Tang, Amal T. Elhaw, Zaineb Javed, Katherine M. Aird, Karthikeyan Mythreye, Rébécca Phaëton, Nadine Hempel.  Gynecologic Oncology,Volume 185,2024, Pages 8-16,ISSN 0090-8258,https://doi.org/10.1016/j.ygyno.2024.02.004.

2023

Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2-driven tumor angiogenesis. Eun-A. Kwak, Tasmia Ahmed, Paola Cruz Flores, Hannah R. Ortiz, Paul R. Langlais, Karthikeyan Mythreye*, Nam Y. Lee*
Cancer Med. 2023 Sep 7.  doi: 10.1002/cam4.6522.  Online ahead of print.

HCK promotes high-grade serous ovarian cancer tumorigenesis through CD44 and NOTCH3 signaling.
Khella CA, Franciosa L, Rodriguez-Rodriguez L, Rajkarnikar R, Mythreye K, Gatza ML.
Mol Cancer Res. 2023 Jun 21:MCR-22-0496. doi: 10.1158/1541-7786.MCR-22-0496. Online ahead of print. PMID: 37342066

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.
Adler F, Anderson A.R.A., Bhushan A, Bogdan P, Bravo-Cordero JJ, Brock A, Chen Y, Cukierman E, DelGiorno KE, Denis GV, Ferrall-Fairbanks M, Gartner Z, Germain R, Gordon DM, Hunter G, Jolly MK, Karacosta LG, Mythreye K, Katira P, Kulkarni RP, Kutys ML, Lander AD, Laughney AM, Levine H, Lou E; Lowenstein PR, Masters KS, Pe'er D, Peyton SR, Platt MO, Purvis JE, Quon G, Richer JK, Riddle NC, Rodriguez A, Snyder JC,  Szeto GL, Tomlin CJ, Yanai I, Zervantonakis I, Dueck HR.  Cell Systems. Volume 14, Issue 4, 19 April 2023, Pages 252-257.

Evolving roles of activins and inhibins in ovarian cancer pathophysiology.
Evans ET, Horst B, Arend RC, Mythreye K.
Am J Physiol Cell Physiol. 2023 Jan 9. doi: 10.1152/ajpcell.00178.2022. Online ahead of print. PMID: 36622068 Review.

2022

Depletion of COPI in cancer cells: the role of ROS in the induction of lipid accumulation, non-canonical lipophagy and apoptosis.
A. Gasparian, M. Aksenova, D. Oliver, E. Levina, R. Doran, M. Lucius, G. Piroli, N. Oleinik, B. Ogretmen, K. Mythreye, N. Frizzell, E. Broude, M.D. Wyatt, and M. Shtutman. Molecular Biology of the Cell. AHEAD OF PRINT. Published Online:12 Oct 2022 https://doi.org/10.1091/mbc.E21-08-0420

Reciprocal epigenetic Sox2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer.
Zainab Shonibare, Mehri Monavarian, Kathleen O’ Connell, Diego Altomare, Abigail Shelton, Shubham Mehta, Renata Jaskula-Sztul, Rebecca Phaeton, Mark D. Starr, Regina Whitaker, Andrew Berchuck, Andrew B Nixon, Rebecca Arend, Nam Y Lee, C. Ryan. Miller, Nadine Hempel, Karthikeyan Mythreye. Cell Reports, VOLUME 40, ISSUE 4, 111066, JULY 26, 2022. DOI:https://doi.org/10.1016/j.celrep.2022.111066

EPDR1 is a Non-canonical Insulin Signaling Effector of Insulin- mediated Angiogenesis Regulated by the Endothelial-specific TGF-b Receptor Complex.
Tasmia Ahmed1, Paola Cruz Flores, Christopher C. Pan, Hannah R. Ortiz, Yeon S. Lee, Paul R. Langlais, Karthikeyan Mythreye* and Nam Y. Lee*. J Biol Chem. 2022 Jul 21;298(9):102297.  doi: 10.1016/j.jbc.2022.102297.  PMID: 35872017  PMCID: PMC9396412  DOI: 10.1016/j.jbc.2022.102297 (* Co-corresponding)

PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance
Kevin Tabury, Mehri Monavarian, Eduardo Listik, Abigail K Shelton, Alex Seok Choi, Roel Quintens, Rebecca C Arend, Nadine Hempel, C Ryan Miller, Balázs Györrfy, Karthikeyan Mythreye. Life Science Alliance Jul 2022, 5 (11) e202201370; DOI: 10.26508/lsa.202201370

Hypoxia-induced inhibin promotes tumor growth and vascular permeability in ovarian cancers.
Ben Horst, Shrikant Pradhan, Roohi Chaudhary, Eduardo Listik, Liz Quintero-Macias, Alex Seok Choi, Michael Southard, Yingmiao Liu, Regina Whitaker, Nadine Hempel, Andrew Berchuck, Andrew B. Nixon, Nam Y. Lee, Yoav I. Henis & Karthikeyan Mythreye.
Commun Biol. 2022 Jun 2;5(1):536.  doi: 10.1038/s42003-022-03495-6


HuR -dependent SOD2 protein synthesis is an early adaptation of ovarian cancer cells in response to anchorage independence Yeon Soo Kim, Jaclyn E. Welles, Priscilla W. Tang, Zaineb Javed, Amal T. Elhaw, Karthikeyan Mythreye, Scot R.Kimball, Nadine Hempel. Redox Biol. 2022 Jul;53:102329.  doi: 10.1016/j.redox.2022.102329.  Epub 2022 May 13.


Emerging perspectives on growth factor metabolic relationships in the ovarian cancer ascites environment
Mehri Monavarian, Amal Taher Elhaw , Priscilla W Tang, Zaineb Javed, Zainab Shonibare, Carly Bess Scalise, Rebecca Arend , Mohit Kumar Jolly, Mary Kathryn Sewell-Loftin, Nadine Hempel, Karthikeyan Mythreye
Semin Cancer Biol 2022 Mar 5;S1044-579X(22)00060-8. doi: 10.1016/j.semcancer.2022.03.004.  Online ahead of print.


Beta-4 spectrin as a stalk cell-intrinsic regulator of VEGF signaling
Eun-A Kwak; Christopher C Pan; Aaron Ramonett; Sanjay Kumar; Paola C Flores; Jeffrey J Lochhead; Paul Langlais; Peter J Mohler; Thomas J Hund; Karthkeyan Mythreye; Nam Y Lee, Ph.D 
Nat Commun. 2022 Mar 14;13(1):1326. doi: 10.1038/s41467-022-28933-1.PMID: 35288568

2021
Regulation of mitochondrial fission by GIPC-mediated Drp1 retrograde transport.Aaron Ramonett, Eun-A Kwak, Tasmia Ahmed, Paola Cruz Flores, Hannah R Ortiz, Yeon Sun Lee, Todd W Vanderah, Tally Largent-Milnes, David F Kashatus , Paul R Langlais, Karthikeyan Mythreye , Nam Y Lee.
Mol Biol Cell 2021 Oct 27;mbcE21060286. doi: 10.1091/mbc.E21-06-0286. Online ahead of print

A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors
Eduardo Listik ,Ben Horst ,Alex Seok Choi, Nam. Y. Lee,Balázs Győrffy, Karthikeyan Mythreye.
PLoS One. 2021 Apr 5;16(4):e0249558. doi: 10.1371/journal.pone.0249558. eCollection 2021.PMID: 33819300 

TGFβ signaling networks in ovarian cancer progression and plasticity
Asha Kumari, Zainab Shonibre, Mehri Monavarian, Rebecca C. Arend, Nam Y. Lee, Gareth J Inman and Karthikeyan Mythreye. 
Clin Exp Metastasis. 2021 Apr;38(2):139-161.  doi: 10.1007/s10585-021-10077-z.

2019-2020
Strength and duration of GIPC-dependent signaling networks as determinants in cancer. 
Tasmia Ahmed, Karthikeyan Mythreye and Nam Y Lee. 
Neoplasia 2020 Dec 24;23(2):181-188. doi: 10.1016/j.neo.2020.12.004

Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells.
Yeon Soo Kim, Piyushi Gupta-Vallur, Victoria M. Jones, Beth L. Worley, Sara Shimko, Dong-Hui Shin, LaTaijah C. Crawford, Chi-Wei Chen, Katherine M. Aird, Thomas Abraham, Trevor G. Shepherd, Joshua I.Warrick,  Nam Y. Lee, Rebecca Phaeton, Karthikeyan Mythreye*, Nadine Hempel*. Oncogene 2020 Feb;39(8):1619-1633doi: 10.1038/s41388-019-1097-7. Epub 2019 Nov 13 

GPX3 supports ovarian cancer progression by manipulating the extracellular redox environment.
Beth L. Worley, Yeon Soo Kim, Jennifer Mardini, Rameez Zaman, Kelly Leon, Piyushi Gupta Vallur, Asvelt Nduwumwami, Joshua I. Warrick, Patrick F. Timmins, Joshua P. Kesterson, Rébécca Phaëton, Nam Y. Lee, Vonn Walter, Lauren Endres, Karthikeyan Mythreye, Katherine M. Aird, Nadine Hempel.  Redox Biology 2019 Jul;25:101051. doi: 10.1016/j.redox.2018.11.009. Epub 2018 Nov 17 

2018
CDK8 selectively promotes the growth of colon cancer metastases in the liver by regulating gene expression of TIMP3 and matrix metalloproteinases.
Liang J, Chen M, Hughes D, Chumanevich AA, Altilia S, Kaza V, Lim CU, Kiaris H, Mythreye K, Pena MM, Broude EV, Roninson IB. 
Cancer Res. 2018 Sep 5. pii: canres.1583.2018. doi: 10.1158/0008-5472.CAN-18-1583.

Deoxycholate Fractionation of Fibronectin (FN) and Biotinylation Assay to Measure Recycled FN Fibrils in Epithelial Cells.
Varadaraj A*, Magdaleno C, Mythreye K. 
Bio Protoc. 2018 Aug 20;8(16). pii: e2972. doi: 10.21769/BioProtoc.2972

Mediator kinase CDK8/CDK19 drives YAP1 dependent BMP4 induced EMT in cancer
Serrao A, Jenkins L.M, Chumanevich.A, Horst B,Liang J, Gatza M.L, Lee N.Y, Roninson I.B,Broude E.V, and Mythreye K. 
Oncogene. 2018 May 21. doi: 10.1038/s41388-018-0316-y. [Epub ahead of print]

TAK1 activation of alpha-TAT1 and microtubule hyperacetylation control AKT signaling and cell growth.
Shah N, Kumar S, Zaman N, Pan CC, Bloodworth JC, Lei W, Streicher JM, Hempel N, Mythreye K, Lee NY. 
Nat Commun. 2018 Apr 27;9(1):1696. doi: 10.1038/s41467-018-04121-y.

Inhibin is a novel paracrine factor for tumor angiogenesis and metastasis.
Singh P, Jenkins LM, Horst B, Alers V, Pradhan S, Kaur P, Srivastava T, Hempel N, Győrffy B, Broude EV, Lee NY, Mythreye K. 
Cancer Res. 2018 Mar 13. pii: canres.2316.2017. doi: 10.1158/0008-5472.CAN-17-2316.

2016
Altering the proteoglycan state of TβRIII /Betaglycan modulates canonical Wnt/β-catenin signaling.
Jenkins LM, Singh P, Varadaraj A, Lee NY, Shah S, Flores HV, O'Connell K, Mythreye K. 
J Biol Chem. 2016 Dec 2;291(49):25716-25728. Epub 2016 Oct 26.

2015
Epigenetic regulation of GDF2 suppresses anoikis in ovarian and breast epithelia.
Varadaraj A, Patel P, Serrao A, Bandyopadhay T,Lee NY, Jazaeri AA, Huang Z, Murphy SK, Mythreye K. 
Neoplasia. 2015 Nov; 17(11):826-38. doi: 10.1016/j.neo.2015.11.003 

Endoglin regulation of Smad2 function mediates beclin1 expression and endothelial autophagy.Pan CC, Shah N, Kumar S, Wheeler SE, Cinti J, Hoyt DG, Beattie CE, An M, Mythreye K, Rakotondraibe LH, Lee NY. 
J Biol Chem.2015 Jun 12;290(24):14884-92. doi: 10.1074/jbc.M114.630178. Epub 2015 Apr 30.

​Other prior select signature papers

TGF-β regulates LARG and GEF-H1 during EMT to impact stiffening response to force and cell invasion.Osborne LD, Li GZ, How T,  O'Brien ET, Blobe GC, Superfine R, Mythreye K. Mol. Biol. Cell 2014 25:22 3528-3540

Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.Knelson EH, Gaviglio AL, Tewari AK, Armstrong MB, Mythreye K*, Blobe GC*. J Clin Invest. 2013 Nov;123(11):4786-98.

Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines.
Swaminathan V*, Mythreye K*, O'Brien ET, Berchuck A, Blobe GC, Superfine R.
Cancer Res. 2011 Aug 1;71(15):5075-80. doi: 10.1158/0008-5472.CAN-11-0247. Epub 2011 Jun 3. (Authorship Note: * equal first)

The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42
Mythreye K, Blobe GC 
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8221-6. doi: 10.1073/pnas.0812879106. Epub 2009 May 1