Hexim‐1 modulates androgen receptor and the TGF‐β signaling during the progression of prostate cancer

Mascareno, Eduardo; Belashov, Ivan A.; Siddiqui, M.A.Q.; Liu, Fang; Dhar-Mascareño, Manya

doi:10.1002/pros.21510

Cited by 14 publications

(10 citation statements)

References 47 publications

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“…HMBA induces differentiation in a variety of cancer cell lines and primary human cancer cell cultures (Marks and Rifkind, 1989). HEXIM1 upregulation is correlated with the transition of cancer cells from proliferation to differentiation, and has been studied in breast cancer (Ketchart et al, 2013; Wittmann et al, 2003, 2005; Yeh et al, 2013) and prostate cancer (Mascareno et al, 2012). 7SK snRNP member LARP7 is mutated in gastric cancer (He et al, 2008; Mori et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

et al. 2016

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Summary Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma.

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Section: Discussionmentioning

confidence: 99%

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

et al. 2016

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“…175 Also a recent study indicated that phosphorylation of serine 158 in HEXIM1 by PKC leads to inhibition of RNA binding in vitro and release of P-TEFb from the 7SK snRNP in cells. 176 HEXIM1 has been shown to associate with the glucocorticoid 177 and androgen receptors 178 and with two proteins involved in p53 metabolism, nucleophosmin and HDM2 179 and these interactions seem to be independent of RNA.…”

Section: The 7sk Snrnpmentioning

confidence: 99%

RNA Polymerase II Transcription Elongation Control

2013

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“…11,14,15 Another group reported on the inhibitory role of HEXIM1 in prostate tumorigenesis. 16 Thus, drug candidates that can enhance the expression of HEXIM1 will have a great application in the treatment of cancer, heart disease, and acquired immunodeficiency syndrome (AIDS).…”

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confidence: 99%

Lead optimization of HMBA to develop potent HEXIM1 inducers

Zhong

Lama

Ketchart

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives inducing Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in LNCaP prostate cancer cells. Several compounds with unsymmetrical structures showed significantly improved activity. Distinct from HMBA, these analogs have increased hydrophobicity and can improve the short half-life of HMBA, which is one of the factors that have limited the application of HMBA in clinics. The unsymmetrical scaffolds of the new analogs provide the basis for further lead optimization of the compounds using combinatorial chemistry strategy.

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Hexim‐1 modulates androgen receptor and the TGF‐β signaling during the progression of prostate cancer

Abstract: Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.

Cited by 14 publications

References 47 publications

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

RNA Polymerase II Transcription Elongation Control

Lead optimization of HMBA to develop potent HEXIM1 inducers

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