Abstract
Regenerating islet-derived type 4 (REG4), a member of the calcium-dependent lectin gene superfamily, is abnormally expressed in various cancers, such as colorectal, gastric, gallbladder, pancreatic, ovarian, prostate, and lung cancer. REG4 is associated with a relatively unfavorable prognosis and clinicopathologic features in cancers, including advanced tumor and nodal stage, histological differentiation, and liver and peritoneal metastasis. Moreover, REG4-positive cancer cells show more frequent resistance to chemoradiotherapy, especially 5-FU-based chemotherapy. REG4 participates in many aspects of carcinogenesis, including cell proliferation, apoptosis, cell cycle, invasion, metastasis, and drug resistance. The underlying mechanisms are complex and involve a series of signaling mediators and multiple pathways. Thus, REG4 may be a potential diagnostic and prognostic biomarker as well as a candidate therapeutic target in cancer patients. In this review, we systematically summarize the advances about the clinical significance, biological functions, and mechanisms underlying REG4 in cancer to provide new directions for future cancer research.
Highlights
The regenerating islet-derived (REG) family genes belong to the calcium-dependent lectin (C-type lectin) gene superfamily
Serum level or tissue protein elevated in pancreatic cancer Elevated in intestinal-type intraductal papillary mucinous neoplasms of the pancreas (IPMNs) Regenerating islet-derived type 4 (REG4)-overexpressing cancer cells resistant to chemoradiotherapy and more frequently local recurrence Pro-proliferation Not independent prognostic factor; Just used in differential diagnosis between pancreatic malignant cancer and chronic pancreatitis Elevated in cancer tissues, especially mucinous carcinomas, intestinal-type; REG4 expression was enhanced by transfection of caudal type homeobox 2 (CDX2)
Most studies have revealed that REG4 overexpression is positively associated with unfavorable clinical parameters, resistance to therapy and poor prognosis, indicating that REG4 is a promising prognostic biomarker and potential therapeutic target in cancer patients
Summary
The regenerating islet-derived (REG) family genes belong to the calcium-dependent lectin (C-type lectin) gene superfamily. High expression of REG4 predicts poor prognosis and drug-resistance by promoting cancer cell proliferation, invasion and anti-apoptosis [18]. REG4 promotes colorectal cancer cell division through Akt/GSK-3b/b-catenin/TCF-4 pathway.
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