ABSTRACT
The aim of this article is to study the regulatory feedback loop between β-catenin and IQ motif containing GTPase activating protein 1 (IQGAP1), as well as the effect of this regulation loop in colon cancer cell proliferation. Western blot was used to detect the expression of IQGAP1 and β-catenin after changing their expression respectively by transfection in SW1116 cells. CCK-8 cell proliferation assay was used to detect the effect of IQGAP1 involved in the proliferation of SW1116 cells promoted by β-catenin. The results of Western blot indicated that β-catenin could positively regulate IQGAP1, while IQGAP1 silencing could up-regulate β-catenin, forming a negative feedback loop. The results of CCK-8 showed that IQGAP1 silencing inhibited β-catenin-mediated proliferation in SW1116 cells. In conclusion, our research reveals a negative regulatory feedback loop between β-catenin and IQGAP1 which has a remarkable effect on the proliferation ability of colon cancer cells.
ABSTRACT
Objective: To explore the molecular mechanism of SAM-and SH3-domain containing 1 (SASH1) which serves as a novel tumor suppressor gene to regulate breast cancer metastasis. Methods: The expressions of SASH1, IQ motif-containing GTPase activating protein 1 (IQGAP1) and E-cadherin in breast cancer tissues were analyzed by immunohistochemistry (IHC). The correlation among SASH1, IQGAP1 and E-cadherin, as well as the association of SASH1 and IQGAP1 expressions with the clinical parameters of breast cancer patients were analyzed, respectively. The recombinant plasmids HAIQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were cloned and transfected into human embryonic kidney HEK-293T cells. The interaction of SASH1 and IQGAP1 was analyzed by immunoprecipitation-Western blotting. Results: In breast cancer tissues, there was a correlation between the expressions of SASH1 and IQGAP1 (P 0.05). The recombinant plasmids HAIQGAP1-pcDNA3.0 and pEGFP-C3-SASH1 were constructed successfully. After these recombinant plasmids were transfected into HEK-293T cells, the interaction between SASH1 and IQGAP1 was found. Conclusion: SASH1 interacts with IQGAP1, and which is closely related to the expression of E-cadherin. Therefore, it is suggested that SASH1 may form a new signaling cascade with IQGAP1 and E-cadherin to regulate breast cancer metastasis.
ABSTRACT
The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.