Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and increases pancreatic cancer growth and metastasis
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Poomy Pandey1,*, Satyanarayana Rachagani2,*, Srustidhar Das2,*, Parthasarathy Seshacharyulu2,*, Yuri Sheinin3, Naava Naslavsky2, Zenggang Pan4, Brittney L. Smith1, Haley L. Peters1,6, Prakash Radhakrishnan1, Nicole R. McKenna1,7, Sai Srinivas Panapakkam Giridharan2,8, Dhanya Haridas2, Sukhwinder Kaur2, Michael A. Hollingsworth1,2,4, Richard G. MacDonald1,2, Jane L. Meza5, Steve Caplan1,2, Surinder K. Batra1,2,4 and Joyce C. Solheim1,2,4
1 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
3 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
4 Department of Pathology, University of Colorado, Aurora, CO, USA
5 Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA
6 Current addresses: Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston TX, USA
7 Current addresses: School of Medicine, University of Virginia, Charlottesville, VA, USA
8 Current addresses: Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
* These authors were equal contributors to this study
Joyce C. Solheim, email:
Keywords: actin, amyloid precursor-like protein 2, metastasis, migration, pancreatic cancer
Received: August 08, 2014 Accepted: December 10, 2014 Published: December 11, 2014
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.
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