Publications

Publications

Integrin-Free Tetraspanin CD151 Can Inhibit Tumor Cell Motility upon Clustering and Is a Clinical Indicator of Prostate Cancer Progression

By:
Contributors: John D. Lewis Research Group

Cancer Res. 2014 Jan 1;74(1):173-87. doi: 10.1158/0008-5472.CAN-13-0275. Epub 2013 Nov 12.

Palmer TD1, Martínez CH, Vasquez C, Hebron KE, Jones-Paris C, Arnold SA, Chan SM, Chalasani V, Gomez-Lemus JA, Williams AK, Chin JL, Giannico GA, Ketova T, Lewis JD, Zijlstra A.

Abstract

Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151(free)) correlates clinically with tumor progression and metastasis. Clustering CD151(free) through its integrin-binding domain promotes accumulation in areas of cell-cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151(free) clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151(free) in prostate cancer correlates with poor patient outcome. When CD151(free) is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151(free) as an independent predictor of survival. Moreover, the detection of CD151(free) can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151(free) with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression.

PubMed

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2018 APCaRI Fall Symposium

Our fall APCaRI 2018 symposium wrapped up on Saturday afternoon after two days of excellent seminars, great food, lots of coffee, bowling, hikes around Banff, get-togethers at the local pub, and beautiful fall weather with minimal snowfall!

The APCaRI meeting was attended by people from across Canada and the USA representing the Alberta Cancer Foundation, Bird Dogs for Prostate Cancer Research, Cross Cancer Institute, DynaLIFE Medical Labs, Edmonton Health City, Entos Pharmaceuticals, Institute of Health Economics, Nanostics Inc, Northern Alberta Urology Centre, Oisin Biotechnologies, PandiaDX, PROSTAID Calgary, Prostate Cancer Centre, Prostate Cancer Support Group, University of Alberta, University of Calgary, Western University, and the Yukon Hospital Corporation.
The invited speakers gave excellent keynote talks that kick-started interesting conversations during the meeting.

Dr. Alison Allan from Western University gave the Friday keynote seminar on developing circulating tumour cells as liquid biospies for early detection of cancers.

Dr. Melina Cimler, CEO of PandiaDX, and Saturday’s keynote speaker, outlined the potentially complex regulatory pathways that molecular diagnostic companies need to navigate when pursuing regulation in the USA.


Thank you to Rume Djebah for organizing the 2018 APCaRI Fall Symposium!

- Perrin Beatty