The Multiple Faces of NANOG in Cancer: A Therapeutic Target to Chemosensitize Therapy-Resistant Cancers

Fatma, Homa; Siddique, Hifzur R.; Maurya, Sudarshan

doi:10.2217/epi-2021-0228

Cited by 13 publications

(6 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TAZ regulates SOX2 and OCT4 expression through phase separation with NANOG NANOG, a master transcriptional regulator of stemness, is linked to cancer progression and chemoresistance 33,34 . Recently, multiple transcriptional coactivators, including TAZ have been shown to activate genes via the phase separation capacity of their activation domains 35,36 .…”

Section: Taz Regulates Chemoresistance and Cancer Stemness In Vitromentioning

confidence: 99%

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation

Liu

Zhu

et al. 2023

Nat Commun

View full text Add to dashboard Cite

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients’ lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.

show abstract

Section: Taz Regulates Chemoresistance and Cancer Stemness In Vitromentioning

confidence: 99%

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation

Liu

Zhu

et al. 2023

Nat Commun

View full text Add to dashboard Cite

show abstract

“…GNA12, encoding for G-alpha subunits of heterotrimeric GTP-binding proteins (G proteins) that link specific cell surface G protein-coupled receptors (GPCRs) to downstream signaling molecules, are intertwined in the largest processes of tumorigenesis and tumor progression [ 43 ] and are interesting molecules to be studied in respect to anti-angiogenic therapy. Another interesting emerged gene is NANOG, encoding for a transcription factor regulating the stemness, and likely involved in drug resistance of cancer cells [ 44 ]. Of note is AGT, encoding for the angiotensinogen, a component of the renin-angiotensin system (RAS), responsible for the final activation of angiotensin-converting enzymes (ACEs) and that has been shown to be involved in cancer biology and progression [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial

Forlani

Cecco

Simeon

et al. 2023

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients. Methods EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation. Results Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib. Conclusions Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach.

show abstract

“…Gastric cancer stemness can be determined by investigating the expression of cell surface markers, namely CD24, CD44, and LGR5, and stemness-related transcriptional factors, namely Nanog and SOX2. Nanog is widely expressed in human cancer and is involved in self-renewal, metastasis, and chemoresistance [ 33 , 34 ]. SOX2 is involved in the maintenance of an undifferentiated cellular phenotype and often leads to increased chemotherapy resistance in cancer [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

et al. 2022

View full text Add to dashboard Cite

Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell–like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.

show abstract

The Multiple Faces of NANOG in Cancer: A Therapeutic Target to Chemosensitize Therapy-Resistant Cancers

Cited by 13 publications

References 95 publications

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation

Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

Contact Info

Product

Resources

About