BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis

Wiel, Clotilde; Gal, Kristell Le; Ibrahim, Mohamed X.; Jahangir, Chowdhury Arif; Kashif, Muhammad; Yao, Haidong; Ziegler, Dorian V.; Xu, Xiufeng; Ghosh, Tanushree; Mondal, Tanmoy; Kanduri, Chandrasekhar; Lindahl, Per; Sayin, Volkan I.; Bergö, Martin O.

doi:10.1016/j.cell.2019.06.005

Cited by 427 publications

(384 citation statements)

References 73 publications

Supporting

Mentioning

362

Contrasting

Order By: Relevance

“…Accumulating data establish BACH1 as a critical facilitator of tumorigenesis and metastasis in breast (U. Lee et al, 2013), colon (Davudian, Shajari, et al, 2016), prostate (Shajari et al, 2018) ovarian and lung (Lignitto et al, 2019;Wiel et al, 2019) cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated levels of BACH1 expression have been linked to a higher risk of breast cancer recurrence in patients (Liang et al, 2012), while association with metastatic spread and poorer prognosis has recently been suggested in the case of human ovarian cancer and lung adenocarcinoma (Lignitto et al, 2019;Wiel et al, 2019). Ectopic expression of BACH1 in breast cancer cells promotes malignancy and metastasis, while its knockdown suppresses these processes.…”

Section: Discussionmentioning

confidence: 99%

“…Lee et al, 2019). In two new studies on lung cancer it was shown that therapeutic intervention that either destabilizes BACH1 (Lignitto et al, 2019) or disrupts its ability to induce glycolysis (Wiel et al, 2019) have the potential to inhibit BACH1 pro-metastatic activity. Targeting the BACH1/VEGFC signaling axis with these inhibitors may potentially be significant therapeutically for various blood and lymphatic vessels pathologies as well.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence point to BACH1, a ubiquitously expressed protein, as a tumor-promoting factor that acts via multiple intracellular signaling cascades (Alvarez & Woolf, 2011;Yun et al, 2011). Recently, higher levels of BACH1 were found to be associated with poor prognosis in human ovarian cancer and to promote lung cancer metastasis (Lignitto et al, 2019;Wiel et al, 2019). BACH1 has been established as a major regulator of breast cancer bone metastasis (Liang et al, 2012) and was postulated as a potential novel therapeutic candidate for cancer treatment ( Numerous reports suggest that, in addition to blood vessel formation, lymphangiogenesis and lymphatic vessel remodeling are pivotal events for tumor expansion and metastatic spread (Stacker et al, 2014).…”

Section: Bach1 Promotes Angiogenesis and Lymphangiogenesis During Tummentioning

confidence: 99%

“…Lee et al, 2014;U. Lee et al, 2013;Liang et al, 2012) and its stabilization in lung adenocarcinoma is associated with increased metastatic dissemination and poor survival (Lignitto et al, 2019;Wiel et al, 2019). To substantiate the pathophysiological relevance of the interaction between BACH1 and VEGFC, we carried out an in silico analysis of publicly available gene-expression data generated by The Cancer Genome Atlas (TCGA) Research Network (https://cancergenome .nih.gov/).…”

Section: The Expression Of Bach1 and Vegfc Correlates During Human Camentioning

confidence: 99%

See 4 more Smart Citations

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Cohen

Tempelhof

Raz

et al. 2019

Preprint

View full text Add to dashboard Cite

Angiogenesis and lymphangiogenesis are key processes during embryogenesis as well as under physiological and pathological conditions. Vascular endothelial growth factor C (VEGFC), the ligand for both VEGFR2 and VEGFR3, is a central lymphangiogenic regulator that also drives angiogenesis. Here we report that members of the highly conserved BACH (BTB and CNC homology) family of transcription factors regulate VEGFC expression, through direct binding to its promoter. Accordingly, downregulation of bach2a hinders blood-vessel formation and impairs lymphatic sprouting in a vegfc-dependent manner during zebrafish embryonic development. In contrast, BACH1-overexpression enhances intratumoral blood-vessel density and peritumoral lymphatic vessel diameter in ovarian and lung mouse tumor models. The effects on the vascular compartment correlate spatially and temporally with BACH1 transcriptional regulation of VEGFC expression. Altogether, our results uncover a novel role for the BACH/VEGFC signaling axis in lymphatic formation during embryogenesis and cancer, providing a novel potential target for therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Bach1 Promotes Angiogenesis and Lymphangiogenesis During Tummentioning

confidence: 99%

Section: The Expression Of Bach1 and Vegfc Correlates During Human Camentioning

confidence: 99%

See 3 more Smart Citations

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Cohen

Tempelhof

Raz

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

Genetic, metabolic and immunological features of cancers with NRF2 addiction

2022

View full text Add to dashboard Cite

Nuclear factor erythroid‐derived 2‐like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental. Many human cancers exhibit persistent NRF2 activation and such cancer cells rely on NRF2 for most of their malignant characteristics, such as therapeutic resistance and aggressive tumourigenesis, and thus fall into NRF2 addiction. The persistent activation of NRF2 confers great advantages on cancer cells, whereas it is not tolerated by normal cells, suggesting that certain requirements are necessary for a cell to exploit NRF2 and evolve into malignant cancer cells. In this review, recent reports and data on the genetic, metabolic and immunological features of NRF2‐activated cancer cells are summarized, and prerequisites for NRF2 addiction in cancer cells and their therapeutic applications are discussed.

show abstract

Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non‐small cell lung cancer

et al. 2021

View full text Add to dashboard Cite

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking—in part due to the difficulty in assessing migration using high‐throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the ‘identification of Migration control genes by differential Expression’. MigExpress exploits the combination of in‐depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration‐associated genes by their differential expression in slow‐ versus fast‐migrating cells. We applied MigExpress to investigate non‐small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration.

show abstract

BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis

Cited by 427 publications

References 73 publications

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Genetic, metabolic and immunological features of cancers with NRF2 addiction

Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non‐small cell lung cancer

Contact Info

Product

Resources

About