We are interested in understanding how aberrations in molecular and cellular mechanisms governing tissue homeostasis may lead to cancer initiation and progression. During past years our laboratory has developed new autochthonous mouse models of high-grade serous ovarian adenocarcinoma, metastatic prostate cancer, luminal subtype B mammary carcinoma and undifferentiated high-grade pleomorphic sarcoma. By using these models we identified the critical roles of p53/miR-34/MET and Rb networks in adult stem cell maintenance and malignant transformation. We have also discovered a novel stem cell niche of the ovarian surface epithelium and have shown that its malignant transformation leads to the most aggressive ovarian cancer, high-grade serous adenocarcinoma. Our current studies focus on identification and characterization of novel cancer-prone stem cell niches of the female reproductive tract and the prostate. We are also pursuing technology-oriented research based on cross-disciplinary collaborations.

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1. Cheng, C-Y. Hwang, C.-I., Corney, D. C., Flesken-Nikitin, A., Long-Chang,J., Öner, G. M., Munroe, R. J., Schimenti, J. C., Hermeking, H., and Nikitin, A. Yu. (2014). miR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment. Cell Reports 6: 1000–1007. PMID: 24630988.
2. Flesken-Nikitin, A., Hwang, C.-I., Cheng, C-Y., Michurina, T. V., Enikolopov, G., and Nikitin, A. Yu. (2013). Ovarian surface epithelium at the junction area contains cancer-prone stem cell niche. Nature 495: 241–245. PMID: 23467088.
3. Hwang, C.-I., Matoso, A., Corney, D. C., Flesken-Nikitin, A., Körner, S., Wang, W., Boccaccio, C., Thorgeirsson, S. S., Comoglio, P. M., Hermeking, H., and Nikitin, A. Yu. (2011). Wild-type p53 controls cell motility and invasion by dual regulation of MET expression. Proc. Natl. Acad. Sci. USA 108:14240-14245. PMID: 21831840.
4. Corney, D. C., Hwang, C., Matoso, A., Vogt, M., Flesken-Nikitin, A., Godwin, A. K., Kamat, A. A., Sood, A. K., Hermeking, H., , Ellenson, L., H., and Nikitin, A. Yu. (2010). Frequent downregulation of miR-34 family in human ovarian cancers. Clin. Cancer Res. 16: 1119–1128. PMID: 20145172.
5. Choi, J., Curtis, S., Roy, D. M., Flesken-Nikitin, A., and Nikitin, A. Yu. (2010). Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency. Am. J. Pathology 177:2645-2658. PMID: 20864684.
6. Cheng, L., Zhou, Z., Flesken-Nikitin, A., Toshkov, I. A., Wang, W., Camps, J., Ried, T., and Nikitin, A. Yu. (2010). Rb inactivation accelerates neoplastic growth and substitutes for recurrent amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated with p53 deficiency. Oncogene 29:5700-5711. PMID: 20676140.
7. Corney, D. C., Flesken-Nikitin, A., Godwin, A. K., Wang, W., and Nikitin, A. Yu. (2007). MicroRNA-34b and -34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433-8438. PMID: 17823410.
8. Zhou, Z., Flesken-Nikitin, A., and Nikitin, A. Yu. (2007). Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res. 67:5683-5690. PMID: 17553900.
9. Zhou, Z., Flesken-Nikitin, A., Corney, D. C., Wang, W., Goodrich, D. W., Roy-Burman, P., and Nikitin, A. Yu. (2006). Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66:7889-7898 PMID: 16912162.
10. Flesken-Nikitin, A., Choi, K.-C., Eng, J. P., Shmidt, E. N., and Nikitin, A. Yu. (2003) Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 63: 3459-3463. PMID: 12839925.

Browse PubMed for a complete listing of Dr. Nikitin's publications

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