MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

Yasuda, Kazuyo; Hirohashi, Yoshihiko; Kuroda, Takafumi; Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide; Hasegawa, Tadashi; Saito, Tsuyoshi; Sato, Noriyuki; Torigoe, Toshihiko

doi:10.1016/j.bbrc.2016.03.004

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…Protein‐protein interaction was analyzed to verify the relationship between NCALD and drug resistance in OC. As can be seen on Figure 5, among the 12 proteins exhibited direct interactions with NCALD according to protein‐protein interaction network, 10 of these proteins including SULF1, ACTN4, AKT1, IKBKE, MYC, NINL, URI1, 7,29 HK2, 30 CAPN1, 31 and FN1 32 make a contribution to the drug resistance in OC. The remaining two proteins CAPNS1 33 and NOLC1 34 are related to drug resistance in other cancers.…”

Section: Resultsmentioning

confidence: 99%

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Dong

Yin

Zhu

et al. 2020

J of Cellular Biochemistry

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Drug resistance, an impenetrable barrier in the treatment of ovarian cancer (OC), is often associated with poor outcomes. Hence, it is urgent to discover new factors controlling drug resistance and survival. The association between neurocalcin delta (NCALD) and cancer drug resistance is poorly understood. Here, we reveal that NCALD messenger RNA expression, probably regulated by DNA methylation and microRNAs, was significantly downregulated in at least three independent microarrays covering 633 ovarian carcinomas and 16 normal controls, which includes the Cancer Genome Atlas (TCGA) ovarian cohort. In the sub‐groups of the TCGA cohort, NCALD was suppressed in 90 platinum‐resistant tissues vs in 197 sensitive tissues. It is consistent with the quantitative reverse transcription polymerase chain reaction results revealing gene downregulation in carboplatin‐resistant SKOV3 and HeyA8 OC cells as compared with that in controls. Low expression of NCALD predicted poor overall survival (OS) in sub‐groups of 1656 patients, progression‐free survival (PFS) in 1435 patients, and post‐progression survival (PPS) in 782 patients according to Kaplan‐Meier plotter covering 1815 OC patients. Comprehensive bioinformatic analyses strongly implicated NCALD in the regulation of drug resistance, probably via competing for endogenous RNA (ceRNA) interactions with CX3CL1 and tumor immune‐microenvironment. NCALD acted as a ceRNA for CX3CL1 in 21 different cancers includes OC according to Starbase. These two genes negatively correlated with tumor purity and positively correlated with infiltration levels of neutrophils and dendritic cells in OC. The combined low expression of NCALD and CX3CL1 showed better prognosis potential for OS, PFS, and PPS in the 1815 OC patients than any of the individually tested genes. In summary, NCALD acts as a ceRNA for CX3CL1, and its downregulation may affect drug resistance and prognosis in OC. Thus, NCALD could be a new therapeutic target for anticancer therapy and a new biomarker for survival prediction in OC.

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Section: Resultsmentioning

confidence: 99%

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Dong

Yin

Zhu

et al. 2020

J of Cellular Biochemistry

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“…Thus, the phaseseparated condensates concentrate the substrates and kinases for highly efficient reactions, leading to the hyperphosphorylation of the C-terminal domain, robust RNA processing and transcriptional elongation. Furthermore, low-complexity domain-low-complexity domain (Dao et al, 2018;Yasuda et al, 2016) ATG Important in carcinogenesis Facilitates autophagy (Chen et al, 2014 ;Fujioka et al, 2020) P62 Essential in modulating tumourigenesis by autophagy…”

Section: Transcriptionmentioning

confidence: 99%

Protein phase separation: A novel therapy for cancer?

Wang

Chen

et al. 2020

British J Pharmacology

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In recent years, phase separation has been increasingly reported to play a pivotal role in a wide range of biological processes. Due to the close relationships between cancer and disorders in intracellular physiological function, the identification of new mechanisms involved in intracellular regulation has been regarded as a new direction for cancer therapy. Introducing the concept of phase separation into complex descriptions of disease mechanisms may provide many different insights. Here, we review the recent findings on the phase separation of cancer‐related proteins, describing the possible relationships between phase separation and key proteins associated with cancer and indicate possible regulatory modalities, especially drug candidates for phase separation, which may provide more effective strategies for cancer therapy.

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“…In a gynaecological cancer (endometrioid adenocarcinoma), ALDH high cells preferentially expressed Hsp27, the over‐expression of which is associated with poor prognosis . Mitogen‐activated kinase (MAPK)13, pituitary tumour‐transforming gene protein‐binding factor (PTTG1IP), calpain 1 (CAPN1) and ubiquilin 2 (UBQLN2) were also found highly expressed in these cells compared with that in ALDH low cells . SOX2, a transcription factor that regulates the Wnt/β‐catenin pathway, is amplified in numerous solid tumours and expressed predominantly in CSCs/TICs .…”

Section: Potential Immune Targeting Of Cscs/ticsmentioning

confidence: 99%

“…127 Mitogen-activated kinase (MAPK)13, pituitary tumour-transforming gene protein-binding factor (PTTG1IP), calpain 1 (CAPN1) and ubiquilin 2 (UBQLN2) were also found highly expressed in these cells compared with that in ALDH low cells. 128 SOX2, a transcription factor that regulates the Wnt/b-catenin pathway, is amplified in numerous solid tumours and expressed predominantly in CSCs/ TICs. 129,130 Interestingly, class I histone deacetylase (HDAC) inhibitors increase the frequency of SP cells with CSC/TIC markers, due to de-differentiation of cancer cells.…”

Section: Oncofetal Antigensmentioning

confidence: 99%

Cancer stem cells as targets for immunotherapy

et al. 2017

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SummaryCurrent cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasize to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypical and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarize some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression.

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MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

Cited by 24 publications

References 24 publications

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Protein phase separation: A novel therapy for cancer?

Cancer stem cells as targets for immunotherapy

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