Laboratory of Protein Structure and Function, Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, 161006, Heilongjiang, China.
Department of gastroenterology, Third Affiliated Hospital, Qiqihar Medical University, Qiqihar, 161000, Heilongjiang, China.
BMC Cancer. 2021 Jan 7;21(1):33. doi: 10.1186/s12885-020-07743-y.
Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated.
Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis.
It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells.
Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.
前梯度-2（AGR2）是一种参与肿瘤发生和癌症进展的原癌基因。AGR2 主要定位于内质网（ER），也是在多种癌症中在外泌体中检测到的分泌蛋白。然而，细胞内和细胞外 AGR2 的生物学功能仍有待阐明。
基于 AGR2 蛋白的生化结构，通过慢病毒介导的稳定过表达系统，生成稳定表达 ER 驻留或分泌 AGR2 的 PANC-1 胰腺癌细胞。在 PANC-1 稳定细胞中评估细胞增殖、迁移、侵袭和存活能力。此外，还测定了 EGFR 的表达和激活，以探讨 AGR2 在胰腺癌发生中的作用的可能机制。
发现分泌型 AGR2 而非 ER 驻留型 AGR2 促进 PANC-1 细胞的增殖、迁移和侵袭。此外，数据表明，ER 驻留型和分泌型 AGR2 均可增强 PANC-1 细胞在衣霉素诱导的内质网应激和吉西他滨处理后的存活能力。然而，在 PANC-1 细胞中未发现 EGFR 表达和激活参与 AGR2 依赖性致癌表型。
分泌型 AGR2 主要参与 PANC-1 胰腺癌细胞的增殖、迁移和侵袭。分泌型和 ER 驻留型 AGR2 均有助于 PANC-1 细胞在挑战性条件下的存活。这些发现深入了解了 AGR2 的不同定位如何促进胰腺癌的生长、转移和药物敏感性。
