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Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression.
Poh, Ashleigh R; Love, Christopher G; Masson, Frederick; Preaudet, Adele; Tsui, Cary; Whitehead, Lachlan; Monard, Simon; Khakham, Yelena; Burstroem, Lotta; Lessene, Guillaume; Sieber, Oliver; Lowell, Clifford; Putoczki, Tracy L; O'Donoghue, Robert J J; Ernst, Matthias.
Affiliation
  • Poh AR; Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Love CG; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Masson F; Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia.
  • Preaudet A; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Tsui C; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Whitehead L; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Monard S; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Khakham Y; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Burstroem L; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Lessene G; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia; Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC 3010, Australia.
  • Sieber O; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia; Department of Colorectal Surgery, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia; School of Biomedical Sciences, Monash University, Clayton, VIC
  • Lowell C; Department of Pathology and Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
  • Putoczki TL; Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia.
  • O'Donoghue RJJ; Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia. Electronic address: robert.od
  • Ernst M; Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia; The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia. Electronic address: matthias.
Cancer Cell ; 31(4): 563-575.e5, 2017 04 10.
Article in En | MEDLINE | ID: mdl-28399411
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Colonic Neoplasms / Proto-Oncogene Proteins c-hck Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2017 Document type: Article Affiliation country: Australia Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Colonic Neoplasms / Proto-Oncogene Proteins c-hck Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2017 Document type: Article Affiliation country: Australia Country of publication: United States