The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights

Sushanta Halder, Seema Parte, Prakash Kshirsagar, Sakthivel Muniyan, Hareesh B. Nair, Surinder K. Batra, Parthasarathy Seshacharyulu

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

The dysregulation of leukemia inhibitory factor (LIF) and its cognate receptor (LIFR) has been associated with multiple cancer initiation, progression, and metastasis. LIF plays a significant tumor-promoting role in cancer, while LIFR functions as a tumor promoter and suppressor. Epithelial and stromal cells secrete LIF via autocrine and paracrine signaling mechanism(s) that bind with LIFR and subsequently with co-receptor glycoprotein 130 (gp130) to activate JAK/STAT1/3, PI3K/AKT, mTORC1/p70s6K, Hippo/YAP, and MAPK signaling pathways. Clinically, activating the LIF/LIFR axis is associated with poor survival and anti-cancer therapy resistance. This review article provides an overview of the structure and ligands of LIFR, LIF/LIFR signaling in developmental biology, stem cells, cancer stem cells, genetics and epigenetics of LIFR, LIFR regulation by long non-coding RNAs and miRNAs, and LIF/LIFR signaling in cancers. Finally, neutralizing antibodies and small molecule inhibitors preferentially blocking LIF interaction with LIFR and antagonists against LIFR under pre-clinical and early-phase pre-clinical trials were discussed.

Original languageEnglish (US)
Article number188737
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1877
Issue number4
DOIs
StatePublished - Jul 2022

Keywords

  • EC359
  • gp130
  • LIF
  • LIFR
  • LIFR-AS1

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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