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PMID: 25576918 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis.

Oncotarget ·Vol. 6 ·No. 4 ·2015-02-10 ·页码 2064-75

Pandey P, Rachagani S, Das S, Seshacharyulu P, Sheinin Y, Naslavsky N, Pan Z, Smith BL, Peters HL, Radhakrishnan P, McKenna NR, Giridharan SS, Haridas D, Kaur S, Hollingsworth MA, MacDonald RG, Meza JL, Caplan S, Batra SK, Solheim JC

Abstract

Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine. Examination of matched human primary tumor-liver metastasis pairs showed that 38.1% of the patients had positive APLP2 expression in both the primary tumor and the corresponding liver metastasis. Stable knock-down of APLP2 expression (with inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to migrate and invade. Loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells. Down-regulation of APLP2 decreased the weight and metastasis of orthotopically transplanted pancreatic tumors in nude mice.

MeSH 主题词
Actin Cytoskeleton/metabolism Amyloid beta-Protein Precursor/genetics,metabolism Animals Anti-Bacterial Agents/pharmacology Cell Line, Tumor Cell Movement Cell Proliferation Down-Regulation/drug effects Doxycycline/pharmacology Female Flow Cytometry Humans Immunoblotting Immunohistochemistry Liver Neoplasms/metabolism,secondary Lung Neoplasms/metabolism,secondary Mice, Nude Nerve Tissue Proteins/genetics,metabolism Pancreatic Neoplasms/genetics,metabolism,pathology RNA Interference Tumor Burden/drug effects,genetics Xenograft Model Antitumor Assays
化学物质
APLP2 protein, human Amyloid beta-Protein Precursor Anti-Bacterial Agents Nerve Tissue Proteins Doxycycline
作者与单位
共 20 位作者,点击展开单位 / ORCID
Pandey Poomy
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Rachagani Satyanarayana
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Das Srustidhar
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Seshacharyulu Parthasarathy
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Sheinin Yuri
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
Naslavsky Naava
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Pan Zenggang
Department of Pathology, University of Colorado, Aurora, CO, USA.
Smith Brittney L
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Peters Haley L
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Current addresses: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston TX, USA.
Radhakrishnan Prakash
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
McKenna Nicole R
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Current addresses: School of Medicine, University of Virginia, Charlottesville, VA, USA.
Giridharan Sai Srinivas Panapakkam
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. | Current addresses: Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Haridas Dhanya
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Kaur Sukhwinder
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Hollingsworth Michael A
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Pathology, University of Colorado, Aurora, CO, USA.
MacDonald Richard G
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Meza Jane L
Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA.
Caplan Steve
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Batra Surinder K
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Pathology, University of Colorado, Aurora, CO, USA.
Solheim Joyce C
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. | Department of Pathology, University of Colorado, Aurora, CO, USA.
Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
Published
2015-02-10
页码
2064-75
Language
English
Country/Region
United States
NLM ID
101532965
基金资助
NIGMS NIH HHS · R01GM087455 · United States
NIGMS NIH HHS · P20 GM103489 · United States
NCI NIH HHS · U54 CA163120 · United States
NCI NIH HHS · U01 CA111294 · United States
NCI NIH HHS · T32CA009476 · United States
NCI NIH HHS · R03 CA167342 · United States
NIGMS NIH HHS · R01 GM087455 · United States
NCI NIH HHS · R03CA169953 · United States
NCI NIH HHS · U01CA111294 · United States
NCI NIH HHS · P50CA127297 · United States
NIGMS NIH HHS · P30 GM106397 · United States
NCI NIH HHS · R01CA133774 · United States
NCI NIH HHS · R03 CA169953 · United States
NCI NIH HHS · P50 CA127297 · United States
NCI NIH HHS · R03CA167342 · United States
NCI NIH HHS · P30 CA036727 · United States
NCI NIH HHS · U54CA163120 · United States
NIGMS NIH HHS · P30GM106397 · United States
NCI NIH HHS · R01 CA133774 · United States
NCI NIH HHS · T32 CA009476 · United States
NCI NIH HHS · P30CA036727 · United States
NIGMS NIH HHS · P20GM103489 · United States
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