CD44 modulates metabolic pathways and altered ROS-mediated Akt signal promoting cholangiocarcinoma progression

Malinee Thanee, Hasaya Dokduang, Yingpinyapat Kittirat, Jutarop Phetcharaburanin, Poramate Klanrit, Attapol Titapun, Nisana Namwat, Narong Khuntikeo, Arporn Wangwiwatsin, Hideyuki Saya, Watcharin Loilome

Research output: Contribution to journalArticlepeer-review

Abstract

CD44 is a transmembrane glycoprotein, the phosphorylation of which can directly trigger intracellular signaling, particularly Akt protein, for supporting cell growth, motility and invasion. This study examined the role of CD44 on the progression of Cholangiocarcinoma (CCA) using metabolic profiling to investigate the molecular mechanisms involved in the Akt signaling pathway. Our results show that the silencing of CD44 decreases Akt and mTOR phosphorylation resulting in p21 and Bax accumulation and Bcl-2 suppression that reduces cell proliferation. Moreover, an inhibition of cell migration and invasion regulated by CD44. Similarly, the silencing of CD44 showed an alteration in the epithelial-mesenchymal transition (EMT), e.g. an upregulation of E-cadherin and a downregulation of vimentin, and the reduction of the matrix metalloproteinase (MMP)-9 signal. Interestingly, a depletion of CD44 leads to metabolic pathway changes resulting in redox status modification and Trolox (antioxidant) led to the recovery of the cancer cell functions. Based on our findings, the regulation of CCA progression and metastasis via the redox status-related Akt signaling pathway depends on the alteration of metabolic profiling synchronized by CD44.

Original languageEnglish
Article numbere0245871
JournalPloS one
Volume16
Issue number3 March
DOIs
Publication statusPublished - 03-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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