Characterization of HMGB1/2 Interactome in Prostate Cancer by Yeast Two Hybrid Approach: Potential Pathobiological Implications

Barreiro-Alonso, Aída; Cámara-Quílez, María; Salamini-Montemurri, Martín; Lamas-Maceiras, Mónica; Vizoso-Vázquez, Ángel; Rodrı́guez-Belmonte, Esther; Quindós-Varela, María; Martínez-Iglesias, Olaia; Figueroa, Angélica; Cerdán, M. Esperanza

doi:10.3390/cancers11111729

Cited by 14 publications

(21 citation statements)

References 108 publications

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“…83 HMGB2 upregulates the androgen receptor (AR)-YY1-mediated transcription and interacts with HOX10 in prostate cancer and subsequently induces proliferation. 81 In breast cancer, HMGB2 transcriptionally regulates glycolytic enzymes lactate dehydrogenase and fructose-bisphosphatase 1 (FBP1) and then regulates the Warburg effect, which provides essential energy for cancer cell's proliferation. 21 Furthermore, HMGB2 can promote p53 or potentiate Wnt/β-catenin pathway, which can be attenuated by anti-human epidermal growth factor receptor 2 antibody via the AKT pathway in HCC.…”

Section: Role Of Hmgb2 In Tumor Proliferation and Meta Stasismentioning

confidence: 99%

Biological functions and theranostic potential of HMGB family members in human cancers

et al. 2020

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The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

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Section: Role Of Hmgb2 In Tumor Proliferation and Meta Stasismentioning

confidence: 99%

Biological functions and theranostic potential of HMGB family members in human cancers

et al. 2020

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“…The interaction between MYH9 and AR was confirmed using CO-IP and MS assays. In fact, several cytoskeletal proteins, such as filamin A ( 25 ), HMGB-1 and HMGB-2 ( 22 ), have been identified as AR cofactors and regulate AR activity. In line with our results, these three AR interactors were also identified as AR pull-down proteins ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

The MYH9 Cytoskeletal Protein Is a Novel Corepressor of Androgen Receptors

et al. 2021

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In the progression of castration-resistant prostate cancer (CRPC), the androgen receptor (AR) that serves as a transcription factor becomes the most remarkable molecule. The transcriptional activity of AR is regulated by various coregulators. As a result, altered expression levels, an aberrant location or activities of coregulators promote the development of prostate cancer. We describe herein results showing that compared with androgen-dependent prostate cancer (ADPC) cells, AR nuclear translocation capability is enhanced in androgen-independent prostate cancer (AIPC) cells. To gain insight into whether AR coregulators are responsible for AR translocation capability, we performed coimmunoprecipitation (CO-IP) coupled with LC-MS/MS to screen 27 previously reported AR cofactors and 46 candidate AR cofactors. Furthermore, one candidate, myosin heavy chain 9 (MYH9), was identified and verified as a novel AR cofactor. Interestingly, the distribution of MYH9 was in both the cytoplasmic and nuclear compartments yet was enriched in the nucleus when AR was knocked down by AR shRNA, suggesting that the nuclear translocation of MYH9 was negatively regulated by AR. In addition, we found that blebbistatin, an inhibitor of MYH9, not only promoted AR nuclear translocation but also enhanced the expression of the AR target gene PSA, which indicates that MYH9 represses nuclear AR signaling. Taken together, our findings reveal that MYH9 appears to be a novel corepressor of AR plays a pivotal role in the progression of CRPC.

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“…Total RNA from the ovarian cell line SKOV-3, was also used to prepare cDNA libraries. Library construction, bait construction and Yeast Two-Hybrid library screening were done as recommended by the vendor of the Matchmaker Gold Yeast Two-Hybrid System (Clontech, Mountain View, CA, USA) and details are already published [ 132 ]. After plasmid rescue, inserts were sequenced with primer T7 (5′-TAATACGACTCACTATAGGG-3′).…”

Section: Methodsmentioning

confidence: 99%

The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response

Cámara-Quílez

Barreiro-Alonso

Vizoso-Vázquez

et al. 2020

Cancers

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High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.

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Characterization of HMGB1/2 Interactome in Prostate Cancer by Yeast Two Hybrid Approach: Potential Pathobiological Implications

Cited by 14 publications

References 108 publications

Biological functions and theranostic potential of HMGB family members in human cancers

Biological functions and theranostic potential of HMGB family members in human cancers

The MYH9 Cytoskeletal Protein Is a Novel Corepressor of Androgen Receptors

The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response

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