KOBV Portal

Hits per page

hits 1 - 10 | 16 hits

Sorting

Online Resource

Spatial epitope barcoding reveals clonal tumor patch behaviors

Rovira-Clavé, Xavier ; Drainas, Alexandros P. ; Jiang, Sizun ; [et al.]

Elsevier BV ; 2022

In: Cancer Cell Vol. 40, No. 11 ( 2022-11), p. 1423-1439.e11

add to watchlist on the watchlist

Details

In: Cancer Cell, Elsevier BV, Vol. 40, No. 11 ( 2022-11), p. 1423-1439.e11

Type of Medium: Online Resource

ISSN: 1535-6108

URL: Article

DOI: 10.1016/j.ccell.2022.09.014

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2074034-7

detail.hit.zdb_id: 2078448-X

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer

Cristea, Sandra ; Coles, Garry L. ; Hornburg, Daniel ; [et al.]

American Association for Cancer Research (AACR) ; 2020

In: Cancer Research Vol. 80, No. 6 ( 2020-03-15), p. 1293-1303

add to watchlist on the watchlist

Details

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 6 ( 2020-03-15), p. 1293-1303

Abstract: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5–ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in vitro and in vivo. Transcriptomics analyses identified a role for the MEK5–ERK5 axis in the metabolism of SCLC cells, including lipid metabolism. In-depth lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, including the mevalonate pathway that controls cholesterol synthesis. Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition of the mevalonate pathway by statins. These data identify a new MEK5–ERK5–lipid metabolism axis that promotes the growth of SCLC. Significance: This study is the first to investigate MEK5 and ERK5 in SCLC, linking the activity of these two kinases to the control of cell survival and lipid metabolism.

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/0008-5472.CAN-19-1027

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2020

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

RB depletion is required for the continuous growth of tumors initiated by loss of RB

Doan, Alex ; Arand, Julia ; Gong, Diana ; [et al.]

Public Library of Science (PLoS) ; 2021

In: PLOS Genetics Vol. 17, No. 12 ( 2021-12-8), p. e1009941-

add to watchlist on the watchlist

Details

In: PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2021-12-8), p. e1009941-

Abstract: The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo . In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo .

Type of Medium: Online Resource

ISSN: 1553-7404

URL: Article

DOI: 10.1371/journal.pgen.1009941

DOI: 10.1371/journal.pgen.1009941.g001

DOI: 10.1371/journal.pgen.1009941.g002

DOI: 10.1371/journal.pgen.1009941.g003

DOI: 10.1371/journal.pgen.1009941.g004

DOI: 10.1371/journal.pgen.1009941.g005

DOI: 10.1371/journal.pgen.1009941.s001

DOI: 10.1371/journal.pgen.1009941.s002

DOI: 10.1371/journal.pgen.1009941.s003

DOI: 10.1371/journal.pgen.1009941.s004

DOI: 10.1371/journal.pgen.1009941.s005

DOI: 10.1371/journal.pgen.1009941.s006

DOI: 10.1371/journal.pgen.1009941.s007

DOI: 10.1371/journal.pgen.1009941.s008

DOI: 10.1371/journal.pgen.1009941.s009

DOI: 10.1371/journal.pgen.1009941.s010

DOI: 10.1371/journal.pgen.1009941.s011

DOI: 10.1371/journal.pgen.1009941.s012

DOI: 10.1371/journal.pgen.1009941.s013

DOI: 10.1371/journal.pgen.1009941.s014

DOI: 10.1371/journal.pgen.1009941.s015

DOI: 10.1371/journal.pgen.1009941.s016

DOI: 10.1371/journal.pgen.1009941.s017

DOI: 10.1371/journal.pgen.1009941.s018

DOI: 10.1371/journal.pgen.1009941.s019

DOI: 10.1371/journal.pgen.1009941.s020

DOI: 10.1371/journal.pgen.1009941.s021

DOI: 10.1371/journal.pgen.1009941.s022

DOI: 10.1371/journal.pgen.1009941.r001

DOI: 10.1371/journal.pgen.1009941.r002

DOI: 10.1371/journal.pgen.1009941.r003

DOI: 10.1371/journal.pgen.1009941.r004

DOI: 10.1371/journal.pgen.1009941.r005

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2021

detail.hit.zdb_id: 2186725-2

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Abstract 2893: IGF2 is essential for tumor initiating cell activity in human colorectal cancer

Dubash, Taronish D. ; Siegl, Christine ; Dieter, Sebastian M. ; [et al.]

American Association for Cancer Research (AACR) ; 2017

In: Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2893-2893

add to watchlist on the watchlist

Details

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2893-2893

Abstract: A small fraction of all cells within individual tumours from colorectal cancer (CRC) patients drives long term tumor growth and metastases in immune-compromised mice. Targeting these tumor-initiating cells (TIC) may improve the long-term outcome in advanced CRC. To identify candidate genes which drive proliferation and survival of TIC, we have performed a large scale high throughput loss of function shRNA screen in three-dimensional TIC enriched patient spheroids. Spheroids were transduced with the barcoded Cellecta decipher library comprising 27,500 shRNAs targeting 5043 genes associated with cell signaling pathways (Module 1). Two weeks later, cells were harvested for DNA isolation, barcode amplification and high-throughput barcode sequencing. Amongst others, we found 5/6 shRNAs targeting Insulin growth factor 2 (IGF2) scoring within a 20% depletion threshold, presenting depletion levels very similar to positive control shRNAs. mRNA expression profiling and qPCR analyses demonstrated low to moderate expression of the IGF2 gene product in the majority of patient spheroid cultures analyzed (n=17). In contrast, two out of 15 patient derived spheroid cultures analyzed demonstrated very pronounced IGF2 overexpression ( & gt;250 fold). Integrative SCNA profiling, expression and TAD profiling using the CESAM algorithm, followed by 4C Seq, demonstrated a tandem duplication of the IGF2 locus in these two patients which interrupts a IGF2 adjacent TAD boundary and results in de novo contact domain formation between the IGF2 promoter and a normally hidden distant super-enhancer. A dual luciferase reporter assay revealed that the hijacked enhancer is functionally active in human CRC cells and thereby may drive unphysiological IGF2 expression following enhancer hijacking. To assess the functional relevance of IGF2 tandem duplications, spheroids were transduced with RFP expressing lentiviral vectors encoding for 3 shRNAs targeting IGF2 as well as control shRNAs targeting EIF3A or scrambled shRNA. Strikingly, IGF2 knockdown led to a marked reduction of RFP+ cells in competitive proliferation assays and markedly reduced viability assessed by ATPlight assay. Moreover, IGF2 knockdown strongly reduced tumor formation following xenotransplantation into immune deficient NSG mice. These data demonstrate that IGF2 is required for survival, proliferation and tumor-initiation of primary human TIC enriched spheroids. Notably, oncogenic miRNA-483 is encoded within intron 8 of IGF2, however, its function in IGF2 locus tandem duplicated cells remains elusive. Understanding the mechanisms of IGF2 dependency and the role of miRNA-483 in this context will be essential for the future development of therapeutic approaches targeting IGF2 expression in this patient subset harbouring tandem-duplications of the IGF2 locus. Citation Format: Taronish D. Dubash, Christine Siegl, Sebastian M. Dieter, Joachim Weischenfeldt, Alexandros P. Drainas, Laura Schwarzmueller, Malgorzata Oles, Balca Mardin, Mikolaj Slabicki, Huber Wolfgang, Martin Schneider, Jan Korbel, Hanno Glimm, Claudia R. Ball. IGF2 is essential for tumor initiating cell activity in human colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2893. doi:10.1158/1538-7445.AM2017-2893

Type of Medium: Online Resource

ISSN: 0008-5472 , 1538-7445

URL: Article

DOI: 10.1158/1538-7445.AM2017-2893

RVK:

XA 36000

RVK:

XA 10000

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2017

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability

Achuthankutty, Divya ; Thakur, Roshan Singh ; Haahr, Peter ; [et al.]

Rockefeller University Press ; 2019

In: Journal of Cell Biology Vol. 218, No. 12 ( 2019-12-02), p. 3943-3953

add to watchlist on the watchlist

Details

In: Journal of Cell Biology, Rockefeller University Press, Vol. 218, No. 12 ( 2019-12-02), p. 3943-3953

Abstract: The ATR kinase is a master regulator of the cellular response to DNA replication stress. Activation of ATR relies on dual pathways involving the TopBP1 and ETAA1 proteins, both of which harbor ATR-activating domains (AADs). However, the exact contribution of the recently discovered ETAA1 pathway to ATR signaling in different contexts remains poorly understood. Here, using an unbiased CRISPR-Cas9–based genome-scale screen, we show that the ATR-stimulating function of ETAA1 becomes indispensable for cell fitness and chromosome stability when the fidelity of DNA replication is compromised. We demonstrate that the ATR-activating potential of ETAA1 is controlled by cell cycle– and replication stress–dependent phosphorylation of highly conserved residues within its AAD, and that the stimulatory impact of these modifications is required for the ability of ETAA1 to prevent mitotic chromosome abnormalities following replicative stress. Our findings suggest an important role of ETAA1 in protecting against genome instability arising from incompletely duplicated DNA via regulatory control of its ATR-stimulating potential.

Type of Medium: Online Resource

ISSN: 0021-9525 , 1540-8140

URL: Article

DOI: 10.1083/jcb.201905064

RVK:

WA 15000

Language: English

Publisher: Rockefeller University Press

Publication Date: 2019

detail.hit.zdb_id: 1421310-2

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect

Nishiga, Yoko ; Drainas, Alexandros P. ; Baron, Maya ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Nature Cancer Vol. 3, No. 11 ( 2022-11-21), p. 1351-1366

add to watchlist on the watchlist

Details

In: Nature Cancer, Springer Science and Business Media LLC, Vol. 3, No. 11 ( 2022-11-21), p. 1351-1366

Abstract: Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the ‘don’t-eat-me’ cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enhances the local antitumor effects of radiotherapy in preclinical models of SCLC. Notably, CD47 blockade also stimulates off-target ‘abscopal’ effects inhibiting non-irradiated SCLC tumors in mice receiving radiation. These abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by radiation and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal antitumor effects were observed in other cancer models treated with radiation and CD47 blockade. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in patients with cancer who suffer from metastatic disease.

Type of Medium: Online Resource

ISSN: 2662-1347

URL: Article

DOI: 10.1038/s43018-022-00456-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 3005299-3

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells

Drainas, Alexandros P. ; Lambuta, Ruxandra A. ; Ivanova, Irina ; [et al.]

Elsevier BV ; 2020

In: Cell Reports Vol. 31, No. 1 ( 2020-04), p. 107465-

add to watchlist on the watchlist

Details

In: Cell Reports, Elsevier BV, Vol. 31, No. 1 ( 2020-04), p. 107465-

Type of Medium: Online Resource

ISSN: 2211-1247

URL: Article

DOI: 10.1016/j.celrep.2020.03.029

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2649101-1

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Visualizing intratumoural heterogeneity with EpicMIBI

Drainas, Alexandros P.

Springer Science and Business Media LLC ; 2023

In: Nature Reviews Cancer Vol. 23, No. 6 ( 2023-06), p. 347-347

add to watchlist on the watchlist

Details

In: Nature Reviews Cancer, Springer Science and Business Media LLC, Vol. 23, No. 6 ( 2023-06), p. 347-347

Type of Medium: Online Resource

ISSN: 1474-175X , 1474-1768

URL: Article

DOI: 10.1038/s41568-023-00569-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2060549-3

detail.hit.zdb_id: 2062767-1

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

Weischenfeldt, Joachim ; Dubash, Taronish ; Drainas, Alexandros P ; [et al.]

Springer Science and Business Media LLC ; 2017

In: Nature Genetics Vol. 49, No. 1 ( 2017-1), p. 65-74

add to watchlist on the watchlist

Details

In: Nature Genetics, Springer Science and Business Media LLC, Vol. 49, No. 1 ( 2017-1), p. 65-74

Type of Medium: Online Resource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/ng.3722

RVK:

XA 10000

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 1494946-5

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

Online Resource

Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells

Coles, Garry L. ; Cristea, Sandra ; Webber, James T. ; [et al.]

Elsevier BV ; 2020

In: Cancer Cell Vol. 38, No. 1 ( 2020-07), p. 129-143.e7

add to watchlist on the watchlist

Details

In: Cancer Cell, Elsevier BV, Vol. 38, No. 1 ( 2020-07), p. 129-143.e7

Type of Medium: Online Resource

ISSN: 1535-6108

URL: Article

DOI: 10.1016/j.ccell.2020.05.003

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2074034-7

detail.hit.zdb_id: 2078448-X

SSG: 12

Bookmarklink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Online Resource

Open Access Request

Availability (electronic / print)

Link to publisher

hits 1 - 10 | 16 hits

Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.

Kooperativer Bibliotheksverbund

Berlin Brandenburg