Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Methods & Resources
    • Archive
    • Subjects
  • Collections
  • Submit
    • Submit a Manuscript
    • Author Guidelines
    • License, Copyright, Fee
    • FAQ
    • Why Submit
  • About
    • About Us
    • Editors & Staff
    • Board Members
    • Licensing and Reuse
    • Reviewer Guidelines
    • Privacy Policy
    • Advertise
    • Contact Us
    • LSA LLC
  • Alerts
  • Other Publications
    • EMBO Press
    • The EMBO Journal
    • EMBO reports
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Rockefeller University Press
    • Journal of Cell Biology
    • Journal of Experimental Medicine
    • Journal of General Physiology
    • Cold Spring Harbor Laboratory Press
    • Genes & Development
    • Genome Research

User menu

  • My alerts

Search

  • Advanced search
Life Science Alliance
  • Other Publications
    • EMBO Press
    • The EMBO Journal
    • EMBO reports
    • EMBO Molecular Medicine
    • Molecular Systems Biology
    • Rockefeller University Press
    • Journal of Cell Biology
    • Journal of Experimental Medicine
    • Journal of General Physiology
    • Cold Spring Harbor Laboratory Press
    • Genes & Development
    • Genome Research
  • My alerts
Life Science Alliance

Advanced Search

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Methods & Resources
    • Archive
    • Subjects
  • Collections
  • Submit
    • Submit a Manuscript
    • Author Guidelines
    • License, Copyright, Fee
    • FAQ
    • Why Submit
  • About
    • About Us
    • Editors & Staff
    • Board Members
    • Licensing and Reuse
    • Reviewer Guidelines
    • Privacy Policy
    • Advertise
    • Contact Us
    • LSA LLC
  • Alerts
  • Follow lsa Template on Twitter
Research Article
Source Data
Transparent Process
Open Access

Integrin α3β1 in hair bulge stem cells modulates CCN2 expression and promotes skin tumorigenesis

View ORCID ProfileVeronika Ramovs, Ana Krotenberg Garcia, Ji-Ying Song, Iris de Rink, Maaike Kreft, View ORCID ProfileRoel Goldschmeding, View ORCID ProfileArnoud Sonnenberg  Correspondence email
Veronika Ramovs
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Veronika Ramovs
Ana Krotenberg Garcia
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ji-Ying Song
2Department of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iris de Rink
3Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maaike Kreft
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roel Goldschmeding
4Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Roel Goldschmeding
Arnoud Sonnenberg
1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Arnoud Sonnenberg
  • For correspondence: a.sonnenberg@nki.nl
Published 18 May 2020. DOI: 10.26508/lsa.202000645
  • Article
  • Figures & Data
  • Info
  • Metrics
  • Reviewer Comments
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1. HB keratinocytes lacking integrin α3β1 stay confined within their niche and contribute normally to hair cycle.

    (A) Overview of the K19 Itga3 KO and WT mouse models. (B) Integrin α3β1 is expressed in Cre-induced GFP-positive keratinocytes of K19 Itga3 WT mice and efficiently deleted in GFP-positive keratinocytes of 7-wk-old K19 Itga3 KO mice 1 wk after tamoxifen treatment (back skin, scale bar: 30 μm). (C) Linage tracing of GFP-positive HB keratinocytes showing localization within their niche in K19 Itga3 KO and WT mice 1 wk after tamoxifen treatment (whole mounts of tail epidermis, scale bar: 200 μm). Linage tracing of up to 4 wk can be found in Fig S1B. (D) Whole mount of tail epidermis of K19 Itga3 WT mouse showing co-localization of Cre-induced GFP-positive cells and K15 marker in HBs (scale bar: 500 μm). (E) Linage tracing of GFP-positive HB SCs Cre-induced in telogen (P21) and followed for up to 4 wk over whole hair cycle (until P49) in the back skin of K19 Itga3 KO and WT mice. Representative images of two to three mice per condition are shown (scale bar: 50 μm).

  • Figure S1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S1. HB keratinocytes lacking integrin α3β1 stay confined within their niche.

    (A) Quantification of the percentage of GFP-positive HFs in the back skin of 7-wk-old K19 Itga3 KO and WT mice 1 wk after tamoxifen treatment. Each dot represents a mouse (mean ± SD, unpaired t test). (B) Linage tracing of GFP-positive HB keratinocytes in K19 Itga3 KO and WT mice at up to 4 wk after tamoxifen treatment (whole mounts of tail epidermis, scale bar: 200 μm).

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2. Epidermal deletion of α3β1 causes de novo expression of K15 outside of HBs.

    (A) Overview of the K14 Itga3 KO and WT mouse models. (B) Whole mounts of tail epidermis show the presence of α3β1-depleted K15-positive keratinocytes in upper parts of hair follicles and IFE of K14 Itga3 KO mice (white arrow heads). Remaining α3β1-positive keratinocytes in K14 Itga3 KO mice are preferentially localized to HBs (scale bar: 100 μm). (C) Staining for integrin α3 shows HB localization of α3β1-positive keratinocytes in the back skin of 7-wk-old K14 Itga3 KO mice. α3β1 is found in all basal keratinocytes of K14 Itga3 WT mice of similar age (scale bar: 50 μm). (D) FACS analysis of keratinocytes isolated from back skin epidermis. The chart shows the percentages of α3-positive HB cells (CD34-positive) in the total α3-positive population. Each dot represents a mouse. Gating strategy can be found in Fig S2A (mean ± SD, unpaired t test, *P < 0.05). (E) GAPDH-normalized relative mRNA expression of K15 is increased in the epidermis of back and tail skin of K14 Itga3 KO compared with WT mice. Each dot represents a mouse and is an average of technical duplicate or triplicate (mean ± SD, unpaired t test, *P < 0.05, **P < 0.005).

    Source data are available for this figure.

    Source Data for Figure 2[LSA-2020-00645_SdataF2.xlsx]

  • Figure S2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S2. Epidermal deletion of α3β1 causes de novo expression of K15 outside of HBs.

    (A) Gating strategy of Fig 2D. (B) Double IHC staining for proliferation marker Ki67 and HB marker K15 shows the absence of proliferation of K15-positive HBs in the back and tail epidermis of K14 Itga3 KO and WT mice. (C) FACS quantification of the HB population (CD34+, α6high) in the back skin of K14 Itga3 KO and WT mice in homeostatic conditions and after short-term DMBA/TPA treatment (mean ± SD, unpaired t test). (D) Gating strategy of Fig S2C.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3. The contribution of HB keratinocytes to newly formed IFE is increased in the absence of α3β1.

    (A, B) H&E staining (left) and quantification (right) of wound healing. (A, B) Wound closure is comparable between K19 Itga3 KO and WT mice, 3 (A) and 5 d (B) after wounding. (A) Each dot represents the average length of the neo-epidermis (black arrows) per wound (mean ± SD, unpaired t test). Wounds of six K19 Itga3 WT and five K19 Itga3 KO mice were analyzed (scale bar: 300 μm). (B) Bars represent the percentage of closed wounds per mouse (mean ± SD). Wounds of four K19 Itga3 WT and four K19 Itga3 KO mice were analyzed (scale bar: 1 mm). (C, D) Immunohistochemistry (IHC) staining for GFP (left) and quantification (right) of GFP-positive area per neo-epidermis of K19 Itga3 KO and WT mice. (C) HB-originating GFP-positive keratinocytes comparably contribute to neo-epidermis in K19 Itga3 KO and WT mice 3 d after wounding (scale bar: 300 μm). Each dot represents the percentage of GFP-positive area per wound (mean ± SD, unpaired t test). Wounds of six K19 Itga3 WT and five K19 Itga3 KO mice were analyzed. (D) 5 d after the wounding, the contribution of the α3β1-deficient HB SCs to the newly formed epidermis is more extensive than that of the α3β1-proficient HB SCs. Each dot represents the percentage of GFP-positive area per wound (mean ± SD, unpaired t test, *P < 0.05). Wounds of five K19 Itga3 WT and four K19 Itga3 KO mice were analyzed.

    Source data are available for this figure.

    Source Data for Figure 3[LSA-2020-00645_SdataF3.xlsx]

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4. The absence of α3β1 in HBs reduces susceptibility of mice to DMBA/TPA–mediated tumorigenesis.

    (A) The number of tumors (left) and tumor burden (right) is decreased in K19 Itga3 KO compared with WT mice submitted to the DMBA/TPA carcinogenesis protocol (mean ± SEM, unpaired t test, *P < 0.05, **P < 0.005, ***P < 0.0005). (B) Representative macro images of K19 Itga3 KO and WT mice at the end of the treatment. (C) Histology of benign papillomas and keratoacanthomas, representing the majority of tumors isolated from K19 Itga3 KO and WT mice.

    Source data are available for this figure.

    Source Data for Figure 4[LSA-2020-00645_SdataF4.xlsx]

  • Figure S3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S3. The deletion of α3β1 in HBs causes reduced tumor size and may promote tumor progression.

    (A) The average tumor size is slightly, but significantly decreased in K19 Itga3 KO compared with WT mice submitted to DMBA/TPA carcinogenesis protocol (mean ± SEM, unpaired t test, *P < 0.05, **P < 0.005, ***P < 0.0005). (B) Histology of progressed tumors at the end of DMBA/TPA treatment: squamous cell carcinoma (SCC), isolated from K19 Itga3 KO and WT mice and keratoacanthomas with carcinomatous changes, isolated from K19 Itga3 WT mouse. Progressed tumors were observed in only one K19 Itga3 KO and three WT mice at the end of the treatment. (C) Histology (left) and quantification (right) of the progressed tumors of seven K19 Itga3 KO and seven WT mice, kept on prolonged TPA treatment for up to additional 10 wk. Five K19 Itga3 KO (one tumor/mouse) and three K19 Itga3 WT (one or two tumors/mouse) mice showed tumor progression. In addition to the SCCs and keratoacanthomas with carcinomatous changes, K19 Itga3 KO mice also developed spindle cell sarcomas and mixed basal SCC.

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5. HB-derived keratinocytes are largely absent from skin tumors.

    (A, B) With rare exceptions, Cre-induced GFP-positive cells represent less than 1% of total tumor mass. (A, B) Representative IHC images stained for GFP and (B) quantification of GFP-positive area in cross sections of tumors, isolated from nine K19 Itga3 KO and eight WT mice. The vast majority of tumors is GFP negative (scale bar: 1 mm). (C) Integrin α3β1 is strongly expressed in all tumors analyzed (scale bar: 1 mm). (D, E) Analysis of GFP-positive area over 10 cross sections, cut every 200 μm of randomly selected tumors from four K19 Itga3 KO and four WT mice. (D) The contribution of GFP-positive HB-originating keratinocytes to tumors, isolated from K19 Itga3 KO is significantly reduced compared with WT mice (mean ± SEM, unpaired t test, *P < 0.05). (E) Most tumors are GFP negative in both, K19 Itga3 KO and WT mice. GFP was detected in 9.6% of K19 Itga3 KO and in 32.3% of K19 Itga3 WT tumors and did not exceed 1% of total tumor mass.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6. α3β1-depleted keratinocytes show an increased differentiation signature and decreased expression of CCN2 during the initiation stage of tumorigenesis.

    (A) GFP-positive Cre-induced HB SCs localize to growing hair follicles (HFs) and, in some cases, to isthmus, infundibulum, and IFE (black arrows) after short-term DMBA/TPA treatment in K19 Itga3 KO and WT mice. Left: IHC staining for GFP (scale bar: 100 μm). Right: quantification of the number of HFs, where GFP-positive cells were observed in the upper parts of HFs and in adjacent IFE. Each dot represents a mouse (mean ± SD, unpaired t test). (B) Heat map of row-scaled significantly differentially expressed protein-coding genes of GFP-positive keratinocytes, isolated from three K19 Itga3 KO and three K10 Itga3 WT mice after short-term DMBA/TPA treatment. Protein-coding genes have an adjusted P < 0.05 and an average normalized expression across all samples >4 (as calculated with Voom) and a logFC > 0.6 between K19 Itga3 WT an KO mice. (C) IF staining (left) and quantification of mean intensity of the signal (right) for CCN2 in GFP-positive HFs after short-term DMBA/TPA treatment. Each dot represents a GFP-positive HF. HFs of five K19 Itga3 KO and six K19 Itga3 WT mice were quantified (mean ± SD, unpaired t test, P < 0.0001).

  • Figure S4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S4. HB-originating α3β1-depleted keratinocytes show decreased expression of CCN2 during the initiation stage of tumorigenesis.

    (A) A heat map showing expression of selected epidermal markers, selected from gene list, in GFP-positive HB-originating keratinocytes, isolated from the skin of short-term DMBA/TPA–treated K19 Itga3 KO and WT mice. (B) IHC staining for GFP and CCN2 in the skin of short-term DMBA/TPA–treated K19 Itga3 KO and WT mice (scale bar: 100 μm). (C) Sparse CCN2-positive cells can be observed in epithelia and stroma of all tumors of K19 Itga3 WT mice (arrow heads). Top: quantification of the CCN2-positive area in cross-section of 127 tumors, isolated from six K19 Itga3 WT mice. CCN2 represents less than 1% of total tumor surface in most tumors. Bottom: representative IHC staining for CCN2 (scale bar: 500 μm). (D) Consecutive section of papilloma, isolated from K19 Itga3 WT mouse, stained for GFP and CCN2. No overlap of the two markers can be observed (scale bar: 500 μm).

  • Figure 7.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 7. CCN2 expression in transformed keratinocytes is α3β1-dependent.

    (A) GAPDH-normalized relative mRNA expression of CCN2 is significantly decreased in non-stimulated as well as IL-6 and TPA-treated α3β1-depleted keratinocytes. The average of up to four independent measurements of technical duplicates of four RNA samples per group (dots) is presented (mean ± SD, Fisher’s LSD test, *P < 0.05, **P < 0.005, ***P < 0.0005, ****P < 0.0001). (B) IF (left) and quantification of the mean intensity (right) of CCN2 in non-stimulated, IL-6, and TPA-treated MSCC Itga3 KO and WT keratinocytes. Expression of CCN2 is α3β1 dependent and increases upon IL-6 and TPA treatment (scale bar: 50 μm). 90 cells imaged over three independent experiments were quantified (mean ± SD, Fisher’s LSD test, P < 0.0001). (C) Representative WB confirming α3β1-dependent and IL-6– and TPA-mediated CCN2 expression. Quantification can be found in Fig S5A.

    Source data are available for this figure.

    Source Data for Figure 7[LSA-2020-00645_SdataF7.pdf]

  • Figure S5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S5. CCN2 expression in transformed keratinocytes is α3β1-dependent.

    (A) Quantification of WB from Fig 7C. Bars represent the mean of five independent experiments (mean ± SD, Fisher’s LSD test, *P < 0.05, **P < 0.005, ***P < 0.0005, ****P < 0.0001). (B) IF images showing co-localization of excreted CCN2 and laminin-332 in the culture of non-treated MSCC Itga3 KO and WT keratinocytes.

  • Figure 8.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 8. CCN2 promotes colony formation and 3D growth of transformed keratinocytes expressing α3β1.

    (A) WB of CCN2 and integrin α3-expression of selected CCN2 KO and control clones. (B) Representative image (top) and quantification (bottom) of colony-formation assay of MSCC Itga3 WT and Itga3 KO cells and MSCC CCN2 KO G1, KO G2, control G1, and control G2 clones. Deletion of α3β1 results in a strong reduction of colony formation and colony size. Moderate reduction of colony formation can be seen upon CCN2 deletion. Quantification of colony size can be found in Fig S6A. Average values of technical triplicates of five independent experiments are presented (mean ± SD, Fisher’s LSD test, *P < 0.05, **P < 0.005, ****P < 0.0001). (C) Representative image (top) and quantification (bottom) of colony-formation assay of MSCC CCN2 KO G1 and KO G2 clones, grown in control conditions or in the presence of 45 ng/ml CCN2, as well as CCN2 WT control G1 and control G2 clones. Treatment with exogenous CCN2 significantly increases colony formation of CCN2 KO clones. Quantification of colony size can be found in Fig S6B. Average values of technical triplicates of four independent experiments are presented (mean ± SD, Fisher’s LSD test, *P < 0.05, **P < 0.005). (D) No differences in the number of colonies can be observed upon CCN2 treatment of Itga3 KO–transformed keratinocytes. Quantification of colony size can be found in Fig S6B. Average values of technical triplicates of four independent experiments are presented (mean ± SD, Fisher’s LSD test, ****P < 0.0001). (E) Quantification (left) and IF as maximum intensity projection (right) of CCN2 expression of MSCC Itga3 WT and KO spheroids, grown in 3D Matrigel matrix for 1 or 7 d (scale bar: 20 μm). The expression of CCN2 is α3β1 dependent, which is particularly prominent at the beginning of spheroid growth. The percentage of CCN2-positive area was quantified from 17 MSCC Itga3 KO and 30 MSCC Itga3 WT spheroids 1 d after seeding and from 15 MSCC Itga3 KO and 27 MSSC WT spheroids 7 d after seeding (mean ± SEM, unpaired t test, *P < 0.05). (F) Spheroid growth in 3D Matrigel is α3β1 dependent and moderately reduced upon CCN2 deletion. Top: bright-filed images of representative spheroids (scale bar: 50 μm). Bottom: size quantification of 60–80 spheroids measured over three to four independent experiments (mean ± SD, Fisher’s LSD test, ****P < 0.0001). (G) 3D growth of CCN2 KO MSCC spheroids shows small but significant increase when cells are seeded with 45 ng/ml of CCN2. Left: bright-filed images of representative spheroids (scale bar: 50 μm). Right: size quantification of 85–90 spheroids measured over three independent experiments (mean ± SD, Fisher’s LSD test, **P < 0.005, ***P < 0.0005 ****P < 0.0001). (H) Seeding Itga3 KO MSCCs with 45 or 180 ng/ml of CCN2 does not impact the 3D growth pf spheroids. Left: bright-filed images of representative spheroids (scale bar: 50 μm). Right: size quantification of 70 spheroids measured over two independent experiments (mean ± SD, one-way ANOVA, P = 0.9491).

    Source data are available for this figure.

    Source Data for Figure 8[LSA-2020-00645_SdataF8.pdf]

  • Figure S6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure S6. CCN2 promotes colony formation and 3D growth of transformed keratinocytes expressing α3β1.

    (A) Quantification of the colony size from colony formation from Fig 8B. Total colonies from three independent experiments were quantified (n = 246–563, mean ± SD). (B) Quantification of the colony size from colony formation from Fig 8C and D. Total colonies from three independent experiments were quantified (n = 166–779, mean ± SD). (C) 3D growth of CCN2 KO MSCC spheroids shows small but significant increase when cells are seeded with 180 ng/ml of CCN2. Left: bright-filed images of representative spheroids (scale bar: 50 μm). Right: size quantification of 90 spheroids measured over three independent experiments (mean ± SD, Fisher’s LSD test, **P < 0.005, ***P < 0.0005, ****P < 0.0001). (D) Whereas seeding MSCC CCN2 G1 clone with CCN2 increases its 3D growth, such effect is not observed when exogenous CCN2 (180 ng/ml) is added when spheroids have already formed 3 d after seeding. Left: size quantification of 90 spheroids measured over two to three independent experiments (mean ± SD, Fisher’s LSD test, ****P < 0.0001). Right: bright-filed images of representative spheroids (scale bar: 50 μm).

Tables

  • Figures
    • View popup
    Table 1.

    List of primary antibodies used, including application, dilution, and source.

    AntigenNameTypeApplicationDilutionSource
    Integrin α3Rabbit pAbWB1:2,000Homemade
    Integrin α3AF2787Goat pAbIF1:100R&D Systems
    Integrin α3AF2787Goat pAbFACS1:100R&D Systems
    Integrin α3sc-374242Mouse mAbIHC1:500Santa Cruz
    Integrin α6-PEeBioGoH3Rat mAbFACS1:200eBioscience
    CCN2E-5Mouse mAbWB1:800Santa Cruz
    CCN2L-20Goat pAbIF, IHC1:100Santa Cruz
    CD34-FITCRAM34Rat mAbFACS1:100eBioscience
    GAPDHCB1001Mouse mAbWB1:1,000Calbiochem
    GFPab6556Rabbit pAbIHC1:2,000Abcam
    Keratin 15MA1-90929Mouse mAbIF, IHC1:200Thermo Fisher Scientific
    Ki67PSX1028Rabbit pAbIHC1:750Monosan
    Laminin-332R14Rabbit pAbIF1:400Kind gift of M Aumailey
PreviousNext
Back to top
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Life Science Alliance.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Integrin α3β1 in hair bulge stem cells modulates CCN2 expression and promotes skin tumorigenesis
(Your Name) has sent you a message from Life Science Alliance
(Your Name) thought you would like to see the Life Science Alliance web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Hair bulge integrin α3β1 and skin cancer
Veronika Ramovs, Ana Krotenberg Garcia, Ji-Ying Song, Iris de Rink, Maaike Kreft, Roel Goldschmeding, Arnoud Sonnenberg
Life Science Alliance May 2020, 3 (7) e202000645; DOI: 10.26508/lsa.202000645

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Hair bulge integrin α3β1 and skin cancer
Veronika Ramovs, Ana Krotenberg Garcia, Ji-Ying Song, Iris de Rink, Maaike Kreft, Roel Goldschmeding, Arnoud Sonnenberg
Life Science Alliance May 2020, 3 (7) e202000645; DOI: 10.26508/lsa.202000645
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
Issue Cover

In this Issue

Volume 3, No. 7
July 2020
  • Table of Contents
  • Cover (PDF)
  • About the Cover
  • Masthead (PDF)
Advertisement

Jump to section

  • Article
    • Abstract
    • Introduction
    • Results
    • Discussion
    • Materials and Methods
    • Data Availability
    • Acknowledgements
    • References
  • Figures & Data
  • Info
  • Metrics
  • Reviewer Comments
  • PDF

Subjects

  • Cancer

Related Articles

  • No related articles found.

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • p14ARF and MDM2 AD inhibit RING activity
  • RECODE for scRNA-seq data
  • Pldo/ZSWIM8 and actin polymerization
Show more Research Article

Similar Articles

EMBO Press LogoRockefeller University Press LogoCold Spring Harbor Logo

Content

  • Home
  • Newest Articles
  • Current Issue
  • Archive
  • Subject Collections

For Authors

  • Submit a Manuscript
  • Author Guidelines
  • License, copyright, Fee

Other Services

  • Alerts
  • Twitter
  • RSS Feeds

More Information

  • Editors & Staff
  • Reviewer Guidelines
  • Feedback
  • Licensing and Reuse
  • Privacy Policy

ISSN: 2575-1077
© 2022 Life Science Alliance LLC

Life Science Alliance is registered as a trademark in the U.S. Patent and Trade Mark Office and in the European Union Intellectual Property Office.