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Publication

Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression.

Cancer cell | 2017

Aberrant activation of the SRC family kinase hematopoietic cell kinase (HCK) triggers hematological malignancies as a tumor cell-intrinsic oncogene. Here we find that high HCK levels correlate with reduced survival of colorectal cancer patients. Likewise, increased Hck activity in mice promotes the growth of endogenous colonic malignancies and of human colorectal cancer cell xenografts. Furthermore, tumor-associated macrophages of the corresponding tumors show a pronounced alternatively activated endotype, which occurs independently of mature lymphocytes or of Stat6-dependent Th2 cytokine signaling. Accordingly, pharmacological inhibition or genetic reduction of Hck activity suppresses alternative activation of tumor-associated macrophages and the growth of colon cancer xenografts. Thus, Hck may serve as a promising therapeutic target for solid malignancies.

Pubmed ID: 28399411 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Bioconductor (RRID:SCR_006442)

Antibodies used in this publication

Associated grants

Agency: NIAID NIH HHS, United States
Id: R01 AI065495
Agency: NIAID NIH HHS, United States
Id: R01 AI068150
Agency: NIAID NIH HHS, United States
Id: R01 AI113272

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This is a list of tools and resources that we have found mentioned in this publication.

Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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CD45, Leucocyte Common Antigen (Dako) (antibody)

RRID:AB_2661839

This monoclonal targets CD45

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APC Rat IgG2a, κ Isotype Ctrl Antibody (antibody)

RRID:AB_2814702

This monoclonal targets

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Monoclonal Mouse Anti-Human Ki-67 Antibody (antibody)

RRID:AB_2687921

This monoclonal targets Ki-67

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Armenian Hamster IgG, Isotype Control, PE Conjugated, Clone HTK888 (antibody)

RRID:AB_326593

This monoclonal targets Armenian Hamster IgG Isotype Control PE Clone HTK888

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APC/Cy7 mouse IgG2a, kappa isotype Ctrl (antibody)

RRID:AB_326477

This isotype control targets not applicable

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Chicken anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (antibody)

RRID:AB_2535861

This polyclonal secondary targets IgG (H+L)

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FITC Mouse IgG2a, k Isotype Ctrl Antibody (antibody)

RRID:AB_2884007

This isotype control targets

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Hck (E1I7F) Rabbit Antidbody (antibody)

RRID:AB_2687496

This monoclonal targets Hck

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CD11b (antibody)

RRID:AB_394775

This monoclonal targets CD11b

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Rat IgG2b, k (antibody)

RRID:AB_10049479

This monoclonal targets Rat IgG2b k

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APC anti-mouse CD206 (MMR) (antibody)

RRID:AB_10900231

This monoclonal targets CD206

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PE/Cy7 rat IgG2a, isotype control (antibody)

RRID:AB_326542

This unknown targets isotype control

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PE/Cyanine7 anti-mouse F4/80 (antibody)

RRID:AB_893478

This monoclonal targets F4/80

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APC/Cyanine7 anti-mouse CD45.2 (antibody)

RRID:AB_830789

This monoclonal targets CD45.2

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PE anti-mouse TCR beta chain (antibody)

RRID:AB_313431

This monoclonal targets TCR beta chain

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APC anti-mouse CD19 (antibody)

RRID:AB_313647

This monoclonal targets CD19

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FITC anti-mouse CD326 (Ep-CAM) (antibody)

RRID:AB_1134107

This monoclonal targets CD326

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EpCAM (VU1D9) Mouse mAb (antibody)

RRID:AB_2098657

This monoclonal targets EPCAM

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Phospho-Stat3 (Tyr705) (M9C6) Mouse mAb (antibody)

RRID:AB_2198588

This monoclonal targets STAT3

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TIE2 antibody [Cl. 16] (antibody)

RRID:AB_2255983

This monoclonal targets TEK

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Goat Anti-Rat IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (antibody)

RRID:AB_141373

This unknown targets Rat IgG (H+L)

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Anti-CD31 antibody (antibody)

RRID:AB_726362

This polyclonal targets CD31

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F4/80 antibody [CI:A3-1] (antibody)

RRID:AB_1140040

This monoclonal targets F4/80 antibody [CI:A3-1]

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MS CD45 PURE MAB 0.5MG 30-F11 (antibody)

RRID:AB_394606

This monoclonal targets CD45

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BrdU (bromodeoxyuridine) (antibody)

RRID:AB_10015222

This unknown targets BrdU (bromodeoxyuridine)

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Lyn Antibody (antibody)

RRID:AB_10694080

This polyclonal targets Lyn

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Phospho-Lyn (Tyr507) Antibody (antibody)

RRID:AB_2138262

This polyclonal targets Phospho-Lyn (Tyr507)

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Phospho-Src (Tyr527) Antibody (antibody)

RRID:AB_331034

This polyclonal targets Phospho-Src (Tyr527)

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ESAT6 (11 G4) (antibody)

RRID:AB_1122638

This monoclonal targets ESAT6 (11 G4)

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Hck (phospho Y410) antibody (antibody)

RRID:AB_942255

This polyclonal targets Hck (phospho Y410) antibody

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Rabbit Anti-S6 Ribosomal Protein Monoclonal Antibody, Unconjugated, Clone 5G10 (antibody)

RRID:AB_331355

This monoclonal targets S6 Ribosomal Protein

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Phospho-S6 Ribosomal Protein (Ser240/244) Antibody (antibody)

RRID:AB_331682

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser240/244)

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p44/42 MAPK (Erk1/2) (137F5) Rabbit mAb (antibody)

RRID:AB_390779

This monoclonal targets p44/42 MAPK (Erk1/2)

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p44/42 MAP kinase (phosphorylated Erk1/2) (antibody)

RRID:AB_331646

This polyclonal targets Erk1/2

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Stat3 (79D7) Rabbit mAb (antibody)

RRID:AB_331269

This recombinant monoclonal targets Stat3

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Phospho-Stat3 (Tyr705) (D3A7) XP Rabbit mAb (antibody)

RRID:AB_2491009

This monoclonal targets Phospho-Stat3 (Tyr705)

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Anti-β-Actin antibody, Mouse monoclonal (antibody)

RRID:AB_476692

This monoclonal targets β-Actin

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IRDye 800CW Goat anti-Mouse IgG (antibody)

RRID:AB_621842

This unknown targets IgG

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Goat Anti-Rabbit IgG IRDye 680 Conjugated (antibody)

RRID:AB_621841

This polyclonal targets IgG

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DLD-1 (cell line)

RRID:CVCL_0248

Cell line DLD-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

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MOLM-13 (cell line)

RRID:CVCL_2119

Cell line MOLM-13 is a Cancer cell line with a species of origin Homo sapiens (Human)

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SW480 (cell line)

RRID:CVCL_0546

Cell line SW480 is a Cancer cell line with a species of origin Homo sapiens (Human)

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MV4-11 (cell line)

RRID:CVCL_0064

Cell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)

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HCT 116 (cell line)

RRID:CVCL_0291

Cell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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