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Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers.
Cancer Res. 2011 Mar 15; 71(6):2162-71.CR

Abstract

Defective expression of LATS2, a negative regulator of YAP oncoprotein, has been reported in cancer of prostate, breast, liver, brain, and blood origins. However, no transcriptional regulators for the LATS2 gene have been identified. Here we report that spontaneous mutation of the transcription factor FOXP3 reduces expression of the LATS2 gene in mammary epithelial cells. shRNA-mediated silencing of FOXP3 in normal or malignant mammary epithelial cells of mouse and human origin repressed LATS2 expression and increased YAP protein levels. LATS2 induction required binding of FOXP3 to a specific sequence in the LATS2 promoter, and this interaction contributed to FOXP3-mediated growth inhibition of tumor cells. In support of these results, reduced expression and somatic mutations of FOXP3 correlated strongly with defective LATS2 expression in microdissected prostate cancer tissues. Thus, defective expression of LATS2 is attributable to FOXP3 defects and may be a major independent determinant of YAP protein elevation in cancer. Our findings identify a novel mechanism of LATS2 downregulation in cancer and reveal an important tumor suppressor relay between the FOXP3 and HIPPO pathways which are widely implicated in human cancer.

Authors+Show Affiliations

Departments of Surgery, Pathology, and Internal Medicine, Division of Immunotherapy, University of Michigan School of Medicine and Cancer Center, Ann Arbor, Michigan 48109, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21278236

Citation

Li, Weiquan, et al. "Identification of a Tumor Suppressor Relay Between the FOXP3 and the Hippo Pathways in Breast and Prostate Cancers." Cancer Research, vol. 71, no. 6, 2011, pp. 2162-71.
Li W, Wang L, Katoh H, et al. Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers. Cancer Res. 2011;71(6):2162-71.
Li, W., Wang, L., Katoh, H., Liu, R., Zheng, P., & Liu, Y. (2011). Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers. Cancer Research, 71(6), 2162-71. https://doi.org/10.1158/0008-5472.CAN-10-3268
Li W, et al. Identification of a Tumor Suppressor Relay Between the FOXP3 and the Hippo Pathways in Breast and Prostate Cancers. Cancer Res. 2011 Mar 15;71(6):2162-71. PubMed PMID: 21278236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers. AU - Li,Weiquan, AU - Wang,Lizhong, AU - Katoh,Hiroto, AU - Liu,Runhua, AU - Zheng,Pan, AU - Liu,Yang, Y1 - 2011/01/28/ PY - 2011/2/1/entrez PY - 2011/2/1/pubmed PY - 2011/7/26/medline SP - 2162 EP - 71 JF - Cancer research JO - Cancer Res. VL - 71 IS - 6 N2 - Defective expression of LATS2, a negative regulator of YAP oncoprotein, has been reported in cancer of prostate, breast, liver, brain, and blood origins. However, no transcriptional regulators for the LATS2 gene have been identified. Here we report that spontaneous mutation of the transcription factor FOXP3 reduces expression of the LATS2 gene in mammary epithelial cells. shRNA-mediated silencing of FOXP3 in normal or malignant mammary epithelial cells of mouse and human origin repressed LATS2 expression and increased YAP protein levels. LATS2 induction required binding of FOXP3 to a specific sequence in the LATS2 promoter, and this interaction contributed to FOXP3-mediated growth inhibition of tumor cells. In support of these results, reduced expression and somatic mutations of FOXP3 correlated strongly with defective LATS2 expression in microdissected prostate cancer tissues. Thus, defective expression of LATS2 is attributable to FOXP3 defects and may be a major independent determinant of YAP protein elevation in cancer. Our findings identify a novel mechanism of LATS2 downregulation in cancer and reveal an important tumor suppressor relay between the FOXP3 and HIPPO pathways which are widely implicated in human cancer. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/21278236/Identification_of_a_tumor_suppressor_relay_between_the_FOXP3_and_the_Hippo_pathways_in_breast_and_prostate_cancers_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=21278236 DB - PRIME DP - Unbound Medicine ER -