AUTHOR=Zhang Junyan , Zhu Zhi , Miao Zhifeng , Huang Xuanzhang , Sun Zhe , Xu Huimian , Wang Zhenning 

TITLE=The Clinical Significance and Mechanisms of REG4 in Human Cancers

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.559230

DOI=10.3389/fonc.2020.559230

ISSN=2234-943X

ABSTRACT=<p>Regenerating islet-derived type 4 (<italic>REG4</italic>), 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. <italic>REG4</italic> 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, <italic>REG4</italic>-positive cancer cells show more frequent resistance to chemoradiotherapy, especially 5-FU-based chemotherapy. <italic>REG4</italic> 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, <italic>REG4</italic> 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 <italic>REG4</italic> in cancer to provide new directions for future cancer research.</p>