PMID- 37849446
OWN - NLM
STAT- MEDLINE
DCOM- 20240105
LR  - 20240106
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 18
IP  - 1
DP  - 2024 Jan
TI  - Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, 
      hypoxia, EMT and mitochondria-related pathways in colorectal cancer.
PG  - 62-90
LID - 10.1002/1878-0261.13535 [doi]
AB  - Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. 
      Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 
      were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor 
      outcome and correlated with epithelial-mesenchymal transition (EMT) and decreased 
      oxidative phosphorylation (OxPhos) in patients; opposite associations were found 
      for isoform 3. Pan-CD44 knockdown (kd) independently impaired primary tumor 
      formation and abrogated distant metastasis in CRC xenografts. The xenograft 
      tumors mainly expressed the clinically relevant CD44 isoforms 3 and 4. Both 
      isoforms were enhanced in the paranecrotic, hypoxic tumor regions but were 
      generally absent in lung metastases. Upon CD44 kd, tumor angiogenesis was 
      increased in the paranecrotic areas, accompanied by reduced hypoxia-inducible 
      factor-1alpha and CEACAM5 but increased E-cadherin expression. Mitochondrial genes 
      and proteins were induced upon pan-CD44 kd, as were OxPhos genes. Hypoxia 
      increased VEGF release from tumor spheres, particularly upon CD44 kd. Genes 
      affected upon CD44 kd in xenografts specifically overlapped concordantly with 
      genes correlating with CD44 isoform 4 (but not isoform 3) in patients, validating 
      the clinical relevance of the used model and highlighting the 
      metastasis-promoting role of CD44 isoform 4.
CI  - (c) 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on 
      behalf of Federation of European Biochemical Societies.
FAU - Everest-Dass, Arun
AU  - Everest-Dass A
AD  - Institute for Glycomics, Griffith University, Gold Coast Campus, Australia.
FAU - Nersisyan, Stepan
AU  - Nersisyan S
AUID- ORCID: 0000-0002-8830-4679
AD  - Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
AD  - Institute of Molecular Biology, The National Academy of Sciences of the Republic 
      of Armenia, Yerevan, Armenia.
AD  - Armenian Bioinformatics Institute (ABI), Yerevan, Armenia.
FAU - Maar, Hanna
AU  - Maar H
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Novosad, Victor
AU  - Novosad V
AD  - Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Schroder-Schwarz, Jennifer
AU  - Schroder-Schwarz J
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Freytag, Vera
AU  - Freytag V
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Stuke, Johanna L
AU  - Stuke JL
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Beine, Mia C
AU  - Beine MC
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Schiecke, Alina
AU  - Schiecke A
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Haider, Marie-Therese
AU  - Haider MT
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Kriegs, Malte
AU  - Kriegs M
AD  - Department of Radiobiology and Radiation Oncology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - Elakad, Omar
AU  - Elakad O
AD  - Institute of Pathology, University Medical Center Gottingen, Germany.
FAU - Bohnenberger, Hanibal
AU  - Bohnenberger H
AD  - Institute of Pathology, University Medical Center Gottingen, Germany.
FAU - Conradi, Lena-Christin
AU  - Conradi LC
AD  - Clinic for General, Visceral and Pediatric Surgery, University Medical Center 
      Gottingen, Germany.
FAU - Raygorodskaya, Maria
AU  - Raygorodskaya M
AD  - Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
FAU - Krause, Linda
AU  - Krause L
AD  - Institute of Medical Biometry and Epidemiology, University Medical Center 
      Hamburg-Eppendorf, Germany.
FAU - von Itzstein, Mark
AU  - von Itzstein M
AD  - Institute for Glycomics, Griffith University, Gold Coast Campus, Australia.
FAU - Tonevitsky, Alexander
AU  - Tonevitsky A
AD  - Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
AD  - Art Photonics GmbH, Berlin, Germany.
FAU - Schumacher, Udo
AU  - Schumacher U
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
AD  - Medical School Berlin, Germany.
FAU - Maltseva, Diana
AU  - Maltseva D
AD  - Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
FAU - Wicklein, Daniel
AU  - Wicklein D
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
AD  - Department of Anatomy and Cell Biology, University of Marburg, Germany.
FAU - Lange, Tobias
AU  - Lange T
AUID- ORCID: 0000-0001-6632-337X
AD  - Institute of Anatomy and Experimental Morphology, University Medical Center 
      Hamburg-Eppendorf, Germany.
AD  - Institute of Anatomy I, Jena University Hospital, Germany.
AD  - Comprehensive Cancer Center Central Germany (CCCG), Jena and Leipzig, Germany.
LA  - eng
GR  - CE140100003/Australian Research Council Centre of Excellence for Nanoscale 
      BioPhotonics/
GR  - 325043972/German Research Foundation/
GR  - ID1196520/National Health and Medical Research Council/
GR  - ID2009677/National Health and Medical Research Council/
GR  - National Research University Higher School of Economics/
PT  - Journal Article
DEP - 20231103
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - 0 (Protein Isoforms)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (CD44 protein, human)
SB  - IM
MH  - Humans
MH  - Heterografts
MH  - Cell Line, Tumor
MH  - *Angiogenesis
MH  - Protein Isoforms/genetics/metabolism
MH  - *Colorectal Neoplasms/pathology
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Hyaluronan Receptors/genetics/metabolism
MH  - Hypoxia/genetics
MH  - Gene Expression Regulation, Neoplastic
PMC - PMC10766209
OTO - NOTNLM
OT  - CD44 isoforms
OT  - HT-29
OT  - colorectal cancer
OT  - metastasis
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/18 06:44
MHDA- 2024/01/05 06:43
PMCR- 2023/11/03
CRDT- 2023/10/18 03:49
PHST- 2023/08/10 00:00 [revised]
PHST- 2023/01/19 00:00 [received]
PHST- 2023/10/12 00:00 [accepted]
PHST- 2024/01/05 06:43 [medline]
PHST- 2023/10/18 06:44 [pubmed]
PHST- 2023/10/18 03:49 [entrez]
PHST- 2023/11/03 00:00 [pmc-release]
AID - MOL213535 [pii]
AID - 10.1002/1878-0261.13535 [doi]
PST - ppublish
SO  - Mol Oncol. 2024 Jan;18(1):62-90. doi: 10.1002/1878-0261.13535. Epub 2023 Nov 3.