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Background: Lamina-associated polypeptides 2 (LAP2) is a nuclear protein that connects the nuclear lamina with chromatin. Although its critical roles in genetic disorders and hematopoietic malignancies have been described, its expression and roles in digestive tract cancers have been poorly characterized. Methods: To examine the expression of LAP2 in patient tissues, we performed immunohistochemistry and real-time PCR. To examine motility of cancer cells, we employed Boyden chamber, wound healing and Matrigel invasion assays. To reveal its roles in metastasis in vivo, we used a liver metastasis xenograft model. To investigate the underlying mechanism, a cDNA microarray was conducted. Results: Immunohistochemistry in patient tissues showed widespread expression of LAP2 in diverse digestive tract cancers including stomach, pancreas, liver, and bile duct cancers. Real-time PCR confirmed that LAP2 beta is over-expressed in gastric cancer tissues. Knockdown of LAP2 beta did not affect proliferation of most digestive tract cancer cells except pancreatic cancer cells. However, knockdown of LAP2 beta decreased motility of all tested cancer cells. Moreover, overexpression of LAP2 beta increased motility of gastric and pancreatic cancer cells. In the liver metastasis xenograft model, LAP2 beta increased metastatic efficacy of gastric cancer cells and mortality in tested mice. cDNA microarrays showed the possibility that myristoylated alanine-rich C kinase substrate (MARCKS) and interleukin6 (IL6) may mediate LAP2 beta-regulated motility of cancer cells. Conclusions: From the above results, we conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2 beta regulates motility of cancer cells and suggest that LAP2 beta may have utility for diagnostics and therapeutics in digestive tract cancers.