Suppressing of Src–Hic-5–JNK–AKT Signaling Reduced GAPDH Expression for Preventing the Progression of HuCCT1 Cholangiocarcinoma

Wen Sheng Wu, Rui Fang Chen, Chuan Chu Cheng, Jia Ling Wei, Chen Fang Lin, Ren In You, Yen Chang Chen, Ming Che Lee, Yen Chang Chen

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Cholangiocarcinoma (CCA) is a malignant neoplasm of the bile ducts, being the second most common type of cancer in the liver, and most patients are diagnosed at a late stage with poor prognosis. Targeted therapy aiming at receptors tyrosine kinases (RTKs) such as c-Met or EGFR have been developed but with unsatisfactory outcomes. In our recent report, we found several oncogenic molecules downstream of RTKs, including hydrogen peroxide clone-5 (Hic-5), Src, AKT and JNK, were elevated in tissues of a significant portion of metastatic CCAs. By inhibitor studies and a knockdown approach, these molecules were found to be within the same signal cascade responsible for the migration of HuCCT1 cells, a conventionally used CCA cell line. Herein, we also found Src inhibitor dasatinib and Hic-5 siRNA corporately suppressed HuCCT1 cell invasion. Moreover, dasatinib inhibited the progression of the HuCCT1 tumor on SCID mice skin coupled with decreasing the expression of Hic-5 and EGFR and the activities of Src, AKT and JNK. In addition, we found a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and several cytoskeletal molecules such as tubulin and cofilin were dramatically decreased after a long-term treatment of the HuCCT1 tumor with a high dose of dasatinib. Specifically, GAPDH was shown to be a downstream effector of the Hic-5/Src/AKT cascade involved in HuCCT1 cell migration. On the other hand, TFK1, another CCA cell line without Hic-5 expression, exhibited very low motility, whereas an ectopic Hic-5 expression enhanced the activation of Src and AKT and marginally increased TFK1 migration. In the future, it is tempting to investigate whether cotargeting Src, Hic-5 and/or GAPDH is efficient for preventing CCA progression in future clinical trials.

Original languageEnglish
Article number2698
Issue number12
Publication statusPublished - Dec 2022


  • cholangiocarcinoma
  • glyceraldehyde-3-phosphate dehydrogenase
  • HuCCT1
  • hydrogen peroxide clone-5
  • Src nonreceptor tyrosine kinase
  • TFK1

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'Suppressing of Src–Hic-5–JNK–AKT Signaling Reduced GAPDH Expression for Preventing the Progression of HuCCT1 Cholangiocarcinoma'. Together they form a unique fingerprint.

Cite this