Associate Professor

Basic Sciences
Division of Microbiology
School of Medicine
Loma Linda University
Loma Linda, CA 92350

Phone:(909) 558-7562
Fax:(909) 558-4035

Research Interest

Cellular plasticity: a cellular strategy to survive in challenging microenvironments.

Cellular plasticity is defined as the ability of the cell to change its phenotype in response to microenvironmental signals. Stem cells are a prototype of cells with high plasticity due to their physiological role in the generation of a variety of different cell types both during development and in tissue regeneration.

Interestingly, most human tumors contain a minor subpopulation of malignant cells with stem cell characteristics and also high plasticity. These cells are known as cancer stem cells (CSCs) or tumor-initiating cells because of their great ability to originate and support tumors.

My lab is studying the mechanism of cell plasticity in various types of breast cancer in order to understand which genes or pathways are responsible for these changes in cell phenotype. We are using four in vitro experimental approaches, either independently or in combination with each other. These approaches are: a) modification of the microenvironment through the use of conditioned media from other cell types; b) overexpress or inhibit genes that are characteristic of another cell phenotype; c) the use of chemicals that modify histone acetylation, thus changing the epigenetic program of the treated cells; and d) growing cells under hypoxia. We pay special attention to modifying genetic programs important in determining the phenotype of breast cancer stem cells.

We used various bioinformatics tools to compare our findings with information contained in databases related to normal and cancer cells.

I am member of the University of  California Riverside (UCR) - Stem Cell Center and of the Inland Empire Stem Cell Consortium.

Selected Publications

  1. McMullen JRW and Soto, U (2022). Newly identified breast luminal progenitor and gestational stem cell populations likely give rise to HER2-overexpressing and basal-like breast cancers. Discover Oncol. 12:38
  2. Ortiz-Hernandez GL, Sanchez-Hernandez ES, Ochoa PT, Elix CC, Alkashgari HR, McMullen JRW, Soto U, Martinez SR, Diaz Osterman CJ, Mahler M, Roy S, Casiano CA (2021). The LEDGF/p75 Integrase Binding Domain Interactome Contributes to the Survival, Clonogenicity, and Tumorsphere Formation of Docetaxel-Resistant Prostate Cancer Cells. Cells, 10:2723, 2021. doi: 10.3390/cells10102723.
  3. Cajigas-Du Ross CK, Martinez SR, Woods-Burnham L, Duran AM, Roy S, Basu A, Ramirez JA, Ortiz-Hernandez GL, Rios-Colon L, Chirshev E, Sanchez-Hernandez ES, Soto U, Greco C, Boucheix C, Chen X, Unternaehrer J, Wang C, and Casiano CA (2018). RNA sequencing reveals upregulation of a transcriptomic program associated with stemness in metastatic prostate cancer cells selected for taxane resistance. Oncotarget, 9: 30363-30384.
  4. Campbell PS, Mavingire N, Khan S, Rowland LK, Wooten JV, Opoku-Agyeman A, Guevara A, Soto U, Cavalli F, Loaiza Perez A, Nagaraj G, Denham LJ, Adeoye O, Jenkins BD, Davis M, Schiff R, and Brantley EJ (2018). AhR ligand Aminoflavone suppresses α6-integrin-Src-Akt signaling to attenuate tamoxifen resistance in breast cancer cells. J Cell Physiol. 234:108-121.
  5. Brantley E, Callero MA, Berardi DE, Campbell P, Rowland L, Zylstra D, Amis L, Yee M, Simian M, Todaro L, Loaiza-Perez A, and Soto U (2016) AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity. Cancer Lett. 376:53-61.
  6. Williams VM, Filippova M, Soto U, and Duerksen-Hughes PJ. (2011) HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol. 6:45-57.
  7. Lao VV, Herring JL, Kim C H, Darwanto A, Soto U and Sowers L (2009) Incorporation of 5-Chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns. Carcinogenesis 30:886-893.
  8. Mc Lean L, Soto U, Agama K, Francis J, Jimenez R, Pommier Y, Sowers L and Brantley E. (2008) Aminoflavone induces oxidative DNA damage and oxidative species-mediated apoptosis in breast cancer cells. Int.J.Cancer 122:1665-1674.
  9. van Riggelen J, Buchwalter G, Soto U, De-Castro Arce J, Zur Hausen H, Wasylyk B and Rösl F.( 2005) Loss of Net as repressor leads to constitutive increased c-fos transcription in cervical cancer cells. J. Biol. Chem. 280:3286-3294.
  10. De Castro-Arce, J., Soto, U., van Riggelen, J., Schwarz, E., zur Hausen, H. and Rösl, F. (2004) Ectopic expression of non-liganded RAR-{beta} abrogates AP-1 activity by selective degradation of c-Jun in cervical carcinoma cells. J Biol Chem. 279: 45408-45416.
  11. Finzer, P., Krueger, A., Stöhr, M., Brenner, D., Soto, U., Kuntzen, C., Krammer, P.H. and Rösl, F. (2004) HDAC-inhibitors trigger type II apoptosis in HPV-positive cells via induction of the E2F-p73 pathway. Oncogene 23:4807-17.
  12. Finzer, P., Ventz, R., Kuntzen, C., Seibert, N., Soto, U. and Rösl, F. (2002) Growth arrest of HPV-positive cells after histone deacetylase inhibition is independent of E6/E7 oncogene expression. Virology 304: 265-273
  13. Hergenhahn, M., Soto, U., Weninger, A., Polack, A., Hsu, C-H., Cheng, A-L. and Rösl, F. (2002) The chemopreventive compound curcumin is an efficient inhibitor of Epstein-Barr virus BZLF-1 transcription in Raji DR-Luc cells. Mol. Car. 33:137-145.
  14. Bachmann, A., Hanke, B., Zawatzky, R., Soto, U., van Riggelen, J., zur Hausen, H. and Rösl F. (2001) Disturbance of tumor necrosis factor alpha-mediated beta interferon signalling in cervical carcinoma cells. J. Virol. 76:280-291.
  15. Finzer, P., Kuntzen, C., Soto, U., zur Hausen, H. and Rösl, F. (2001) Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in cervical carcinoma cells circumventing human papillomavirus oncogene expression. Oncogene 20:4768-4776.
  16. Finzer, P., Soto, U., Delius, H., Patzelt, A., Coy, J.F., Pustka, A.,  zur Hausen, H. and Rösl, F. (2000) Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: The role of the chromatin structure and AP-1 composition. Oncogene 19: 3235-3244.
  17. Soto, U., Denk, C., Finzer, P., Hutter, K.J., zur Hausen, H. and Rösl, F. (2000) Genetic complementation to non-tumorigenicity in cervical carcinoma cells correlates with alterations in AP-1 composition. Int. J. Cancer 86: 811-817.
  18. Soto, U., Das, B.C., Lengert, M., Finzer, P., zur Hausen, H. and Rösl, F. (1999) Conversion of HPV 18 positive non-tumorigenic HeLa-fibroblast hybrids to invasive growth involves loss of TNF-α mediated repression of viral transcription and modification of the AP-1 transcription complex. Oncogene 18: 3187-3198.