The role of IL-11 in triple negative breast cancer

2021 Honours opportunity

Supervisors: Dr Ashwini Chand and Dr Sarah Bennett

Group: Cancer Therapeutics Development

Subjects prerequisites:MED3LAB, MED3PRJ and/or GEN3LAB

Diagnoses of triple negative breast cancer (TNBC) account for ~15-20% of all breast cancers and is often associated with metastasis and poor patient survival outcomes. It is characterised by an absence of the Estrogen Receptor (ER) and Progesterone Receptor (PR) and no amplification of the HER2 receptor. This renders TNBC insensitive to hormonedirected therapies and limited treatment options exist beyond cytotoxic chemotherapy, which has a high rate of early relapse. Therefore, there is an urgent need to develop a better understanding of the molecular drivers of TNBC in order to develop more treatment options.

Our previous work has identified Interleukin 11 (IL-11), a member of the IL-6 family of cytokines, as a potential driver of TNBC progression and metastasis. An analysis of publicly available datasets reveals IL-11 levels are positively correlated with disease progression and metastatic spread to the bone. To mediate protumourigenic signalling, IL-11 complexes with its receptor (IL-11RA) and the co-receptor, gp130 to phosphorylate the Signal Transducer and Activator of Transcription 3 (STAT3). Activation of STAT3 in the cancers drives cancer hallmarks including proliferation, cell survival, angiogenesis and metastasis.

This project will focus on understanding cytokine-dependent pathways in breast cancer progression and metastasis. We have generated human TNBC cell lines lacking IL-11 and IL-11RA expression using CRISPR-Cas9 directed knockdown. The aim of this honours project will be to characterise these cell lines as follows:

  1. Determine binding of the downstream signal transducer STAT3 to target genes which induce proliferation and metastasis using ChIP-seq analysis.
  2. Validate the expression of target genes at the mRNA (qPCR) and protein (western blot) level.
  3. Functionally determine the effect of IL-11 and IL-11RA knockdown in vitro using proliferation, migration and invasion assays.

The student taking on this project will gain an understanding of the underlying concepts of cancer biology. They will be exposed to a large range of molecular biology techniques (listed above), which are broadly applicable to cancer biology. The results of this study will contribute directly to the development of targeted therapies to improve outcomes for TNBC patients.

The work at ONJCRI/La Trobe School of Cancer Medicine will take place in laboratory setting that has access to patient material and focuses on clinically relevant aspects in the treatment of cancer patients.

 

How do I apply?

Please complete and return your Ranked Entry Project Selection Form (available in the 2021 projects booklet) by 5pm Friday 6 November 2020 to I.Poon@latrobe.edu.au

 

How do I find out more?
Discover more about La Trobe University’s School of Molecular Sciences/LIMS Honours opportunities
Contact the LTU Honours Coordinator, Dr Ivan Poon
Phone: 03 9479 6488
E-mail: I.Poon@latrobe.edu.au