American Association for Cancer Research
00085472can120777-sup-f3_1070k.pdf (1.05 MB)

Supplementary Figure 3 from Functional Interaction of Tumor Suppressor DLC1 and Caveolin-1 in Cancer Cells

Download (1.05 MB)
journal contribution
posted on 2023-03-30, 21:33 authored by Xiaoli Du, Xiaolan Qian, Alex Papageorge, Aaron J. Schetter, William C. Vass, Xi Liu, Richard Braverman, Ana I. Robles, Douglas R. Lowy

PDF file - 1MB, Expression of CAV1 or the combination of low CAV1 with low DLC1 do not affect the prognostic significance of lung cancer patients in Director's challenge cohort



Deleted in liver cancer 1 (DLC1), a tumor suppressor gene frequently inactivated in non–small cell lung cancer (NSCLC) and other malignancies, encodes a multidomain protein with a RhoGTPase-activating (RhoGAP) domain and a StAR-related lipid transfer (START) domain. However, no interacting macromolecule has been mapped to the DLC1 START domain. Caveolin-1 (CAV-1) functions as a tumor suppressor in most contexts and forms a complex with DLC1. Here, we have mapped the region of DLC1 required for interaction with CAV-1 to the DLC1 START domain. Mutation of the DLC1 START domain disrupted the interaction and colocalization with CAV-1. Moreover, DLC1 with a START domain mutation failed to suppress neoplastic growth, although it negatively regulated active Rho. CAV-1 and DLC1 expression levels were correlated in two public datasets of NSCLC lines and in two independent publicly available mRNA expression datasets of NSCLC tumors. Clinically, low DLC1 expression predicted a poor clinical outcome in patients with lung cancer. Together, our findings indicate that complex formation between the DLC1 START domain and CAV-1 contributes to DLC1 tumor suppression via a RhoGAP-independent mechanism, and suggest that DLC1 inactivation probably contributes to cancer progression. Cancer Res; 72(17); 4405–16. ©2012 AACR.

Usage metrics

    Cancer Research



    Ref. manager