HMGA2 Stabilizes hnRNPK to Drive YAP-Dependent Liver Metastasis in Pancreatic Cancer.
- 1Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
- 2State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, China.
Abstract
Pancreatic cancer (PC) is a highly aggressive malignant neoplasm with a propensity for liver metastasis (LM), which significantly contributes to poor patient prognosis, but its molecular mechanism remains incompletely elucidated. In this study, we demonstrated that high mobility group protein A2 (HMGA2) is markedly elevated in LM tissues and circulating tumor cells (CTCs) of PC patients. Mechanistically, HMGA2 binds to heterogeneous nuclear ribonucleoprotein K (hnRNPK) via "AT-hook" functional motif, suppressing its ubiquitination to block proteasomal degradation. This interaction promotes the transcriptional activation of Yes-associated protein (YAP) by facilitating hnRNPK binding to the YAP promoter and thereby enhancing metastatic potential of PC. Functional assays validate that hnRNPK mediates HMGA2's pro-metastatic function, and YAP acts as the indispensable downstream effector of this cascade. Our findings establish the HMGA2/hnRNPK-YAP axis as a critical regulator of LM and propose targeting this pathway as a promising therapeutic strategy for metastatic PC.
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BibTeX
@article{xie2026hmga2,
title = {{HMGA2 Stabilizes hnRNPK to Drive YAP-Dependent Liver Metastasis in Pancreatic Cancer.}},
author = {Yu Xie and Hexing Hang and Haobai Liu and Nannan Wang and Chengzhi Wang and Yifei Yang and Lei Fang and Yudong Qiu and Hao Cheng},
journal = {International journal of biological sciences},
year = {2026},
month = oct,
doi = {10.7150/ijbs.133139},
url = {https://europepmc.org/article/MED/42910299},
note = {CC BY},
}
RIS
TY - JOUR
TI - HMGA2 Stabilizes hnRNPK to Drive YAP-Dependent Liver Metastasis in Pancreatic Cancer.
AU - Yu Xie
AU - Hexing Hang
AU - Haobai Liu
AU - Nannan Wang
AU - Chengzhi Wang
AU - Yifei Yang
AU - Lei Fang
AU - Yudong Qiu
AU - Hao Cheng
PY - 2026
DA - 2026/10/02
JO - International journal of biological sciences
DO - 10.7150/ijbs.133139
UR - https://europepmc.org/article/MED/42910299
AB - Pancreatic cancer (PC) is a highly aggressive malignant neoplasm with a propensity for liver metastasis (LM), which significantly contributes to poor patient prognosis, but its molecular mechanism remains incompletely elucidated. In this study, we demonstrated that high mobility group protein A2 (HMGA2) is markedly elevated in LM tissues and circulating tumor cells (CTCs) of PC patients. Mechanistically, HMGA2 binds to heterogeneous nuclear ribonucleoprotein K (hnRNPK) via "AT-hook" functional motif, suppressing its ubiquitination to block proteasomal degradation. This interaction promotes the transcriptional activation of Yes-associated protein (YAP) by facilitating hnRNPK binding to the YAP promoter and thereby enhancing metastatic potential of PC. Functional assays validate that hnRNPK mediates HMGA2's pro-metastatic function, and YAP acts as the indispensable downstream effector of this cascade. Our findings establish the HMGA2/hnRNPK-YAP axis as a critical regulator of LM and propose targeting this pathway as a promising therapeutic strategy for metastatic PC.
SN - 1449-2288
ER -