Probing MALAT1 in Collective Cancer Invasion
Open Access
- Author:
- Zhu, Ninghao
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 04, 2022
- Committee Members:
- William Hancock, Major Field Member
Pak Kin Wong, Chair & Dissertation Advisor
Zhi-Chun Lai, Outside Unit & Field Member
Spencer Szczesny, Major Field Member
Daniel Hayes, Program Head/Chair - Keywords:
- metastasis
lncRNA
bladder cancer
single cell analysis
biosensor - Abstract:
- Unveiling the mechanisms of cancer invasion and predicting the progression of cancer invasion are two vital directions to mitigate the healthcare burden from cancer invasion. Cancer cells invade collectively with leader-follower organization. However, how leader cells are regulated during the dynamic invasion process remains poorly understood. Using a FRET nanobiosensor that tracks long noncoding RNA (lncRNA) dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that lncRNA MALAT1 is dynamically regulated in the invading fronts of cancer cells and patient-derived organoids. The abundance, diffusivity, and distribution of MALAT1 transcripts are distinct between leader and follower cells. MALAT1 expression increases when a cell acquires the leader cell role and decreases when the migration process stops. Transient knockdown of MALAT1 prevents the formation of leader cells and abolishes the migration of cancer cells. Combining the MALAT1 biosensing with a chimeric invasion assay, we analyzed the invasiveness of transurethral resection of bladder tumor samples. The human dissociated bladder tumor cells of various cancer stages show different levels of dissemination after self-assembly on the CIA surface, correlating with the MALAT1 expression. Taken together, this work provides a promising biosensing platform for bladder cancer prognosis.