Overexpression of RhoGDI2 Correlates with Tumor Progression and Poor Prognosis in Colorectal Carcinoma

Li, Xianzheng; Wang, Jianmei; Zhang, Xiaojing; Zeng, Yuanfeng; Li, Liang; Ding, Yan‐Qing

doi:10.1245/s10434-011-1944-4

Cited by 19 publications

(22 citation statements)

References 34 publications

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“…However, increasing evidence shows that D4-GDI is also expressed in nonhematopoietic neoplasms [5,9,11,20,27,37,38]. The elevated D4-GDI expression has been associated with tumor growth and malignant progression of ovarian [37], lung [27], gastric [5] and colorectal cancers [20]. In line with these observations, we have previously shown that D4-GDI is highly expressed in a panel of 8 breast cancer cell lines but not in normal mammary epithelial cells [45].…”

Section: Discussionmentioning

confidence: 56%

“…In support of this notion, depletion of D4-GDI in MDA-MB-231 breast cancer cells suppressed invasive phenotypes both in vitro and in animal models [44,45]. Likewise, overexpression of D4-GDI in colorectal cancer cells promoted cell proliferation and in vitro motility and invasion [20]. On the other hand, our results show that the majority (78%) of malignant breast cancer and all metastatic lymph nodes samples had little or undetectable D4-GDI immunoreactivity which is in agreement with reports by others [12,25,33].…”

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Association of D4-GDI expression with breast cancer progression

Rosado

Rodriguez‐Canales

Zhang

2012

CBM

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Abstract. D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 66%

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Association of D4-GDI expression with breast cancer progression

Rosado

Rodriguez‐Canales

Zhang

2012

CBM

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“…By contrast, another study suggested that the cleavage of RhoGDI2 by caspase-3 is not a functionally irrelevant effect of caspase activation during apoptosis but rather expedites the progression of the apoptotic process (23). Unlike bladder cancer and lymphoma cells, RhoGDI2 was reported as an oncogene in breast, colon and gastric cancer cells (9,10,24). A Korean group reported that RhoGDI2 confers resistance to cisplatin-induced apoptosis in gastric cancer cells by upregulating Bcl-2 expression and activating PLCγ (19,25).…”

Section: Discussionmentioning

confidence: 99%

RhoGDI2 confers resistance to 5-fluorouracil in human gastric cancer cells

Zheng

et al. 2012

Oncology Letters

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Abstract. Resistance to 5-fluorouracil (5-FU) in patients with gastric cancer is a serious therapeutic problem and major efforts are underway to understand the underlying mechanisms. We have previously identified RhoGDI2 as a contributor to 5-FU resistance in colon cancer cells using 2D electrophoresis and mass spectrometry and the current study aimed to further investigate this role. The expression of RhoGDI2 in seven gastric cancer cell lines was positively correlated with resistance to 5-FU. Lower 5-FU sensitivity of isolated tumor cells from patients with gastric cancer was also associated with higher RhoGDI2 expression. Ectopic expression of RhoGDI2 in gastric cancer cells increased the resistance to 5-FU and reverted low dose 5-FU-induced G2/M phase arrest without affecting the population of sub-G1 cells. Overall, these findings suggest that RhoGDI2 is associated with 5-FU resistance and is a potential therapeutic target for enhancing chemotherapy efficacy in gastric cancer.

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“…The other 14, most of which are already known to be involved in cancer (TGFB2, NTF3 (29), UACA (30), SFRP4 (31), and ULBP2 (32), were overexpressed. Another gene like ARHGDIB has been associated with prognosis (33,34) and cisplatin resistance (35). Selected genes were validated at the protein level ( Supplementary Fig.…”

Section: Refining the Fpg Signature: Developing A Classifiermentioning

confidence: 99%