First person – Lei Qi Free

Lei Qi

How would you explain the main findings of your paper in lay terms?

The most common cause of cancer patient death is metastatic disease to various organs. Cancer metastasis depends on cancer cell adaption to an environment that is different from its origin. Integrin α6β4 works as an anchor, helping cells embed into the new tissue. It also works as a sensor detecting the external information and re-shaping the cancer cell so it is prepared for interactions with the extracellular matrix (ECM). In my research, integrin α6β4 was found to utilize both laminin and fibronectin as key ECM components, enhance cell adhesion and invasive growth, and associate with other integrin family members, such as integrin αV and β1. This association possibly leads to an interaction of α6β4 with focal adhesions and intermediate filaments proteins, such as vimentin, and induces α6β4-related signal transduction, such as FAK phosphorylation. We also found that the α6β4–focal adhesion–vimentin complex is highly mobile in a matrix comprising laminin1 and fibronectin. Interruption of the assembly of this complex abolished α6β4-mediated enhanced cell migration and invasive cell growth. My research thus unveiled the potency of α6β4 in different matrices, illustrating its important role in breast cancer cell metastasis.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Previous research on integrin α6β4 was focused on its role in hemidesmosomes, which are typically found in keratinocytes, but there are different aspects to α6β4 function in breast cancer cells. However, it is difficult to study α6β4 independently from other integrin family members and factors, a problem our lab has come across before. In this study, we first distinguished the reactions of α6β4 to two major ECM components (laminin 1 and fibronectin), which were greatly different. We also clarified the relationship of other integrin family members and plectin with α6β4 during the assembly of the α6β4–focal adhesion–vimentin linkage by using CRISPR gene editing, which is more efficient than former technologies, like shRNA and siRNA.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

The first decisive observation is always impressive. In this project, it was the first focal-adhesion-like structure I saw under the TIRF microscope, where cells were cultured with fibronectin by chance, and α6β4 labeled with a EGFP tag was spotted on the cell surface. This was unexpected, because we had a difficult time to visualize α6β4 before we eventually abandoned α6β4 antibody staining.

Why did you choose Journal of Cell Science for your paper?

Real research is not only represented by impact factor; we felt the journal is a decent journal in cell biology and molecular biology and is the best choice for our research.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Dr. K. L. O'Connor is the best mentor I have ever met. She is always an inspiration to my research.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

It is so hard for a physician to face the death of his patient, being so helpless. Research is good for me because I feel this is the hope for all cancer patients.

Who are your role models in science? Why?

Nikola Tesla. It is because of his attitude and consistency of his research despite the external pressure from high above, even non-scientific or just politics, which are also still present now.

What's next for you?

I am continuing to work on cancer cell adhesion-related epigenetics and metabolism research in the lab of Kathleen L. O’Connor.

Tell us something interesting about yourself that wouldn't be on your CV

I enjoy leaning about history of Europe and east Asia. I also enjoy playing tennis and basketball, which make me feel I am still in my 20s. Music is also a favorite past-time, which can make me feel the world is so nice.