2D-DIGE and MALDI TOF/TOF MS analysis reveal that small GTPase signaling pathways may play an important role in cadmium-induced colon cell malignant transformation

Lü, Jian; Zhou, Zhongping; Zheng, Jianzhou; Zhang, Zhuyi; Lu, Rongzhu; Liu, Hanqing; Shi, Haifeng; Tu, Zhigang

doi:10.1016/j.taap.2015.07.020

Cited by 12 publications

(5 citation statements)

References 43 publications

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“…Experimental evidence further demonstrates that by suppressing DNA mismatch repair mechanism, Cd acts a mutagen [20] and might therefore contribute to CRC. Moreover, Cd was shown to induce transformative and carcinogenic effects in human colorectal cells CRL-1807 and a xenograft animal model [21].…”

Section: Introductionmentioning

confidence: 99%

Cadmium Induces Migration of Colon Cancer Cells: Roles of Reactive Oxygen Species, P38 and Cyclooxygenase-2

Naji

Issa

Eid

et al. 2019

Cell Physiol Biochem

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Section: Introductionmentioning

confidence: 99%

Cadmium Induces Migration of Colon Cancer Cells: Roles of Reactive Oxygen Species, P38 and Cyclooxygenase-2

Naji

Issa

Eid

et al. 2019

Cell Physiol Biochem

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“…Therefore, the renal proximal tubular cells are excellent model to study Cd-induced cytotoxicity and renoprotective strategies 6 , 7 . Exposure to Cd could induce various cellular responses such as carcinogenesis, necrosis, apoptosis, proliferation and autophagy 8 – 10 . Previous studies had reported that Cd induced apoptotic cell death in the renal proximal tubule cells, i.e.…”

Section: Introductionmentioning

confidence: 99%

Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells

Dai

Liu

et al. 2018

Sci Rep

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Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms. Cd induced intracellular Ca2+ elevation through phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38 mitogen-activated protein kinases (MAPK) activation and suppressing extracellular signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell death and inhibit cell proliferation. Cd induced p38 activation also contribute to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467 reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also increased cell proliferation and restored autophagic flux by switching p38 to ERK pathway. The identification of the activation of CaSR-mediated protective pathway in renal cells sheds light on a possible cellular protective mechanism against Cd-induced kidney injury.

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“…Cells treated for 48 hr were used for detection of centrosome amplification, and those treated for 30 hr were used for proteomic and western blot analyses. Colon cells were used in the study as cadmium can cause colon cell malignant transformation (Lu et al, 2015). MTT assay was used to quantify cell viability after 48 hr of treatment (0, 10, 20, and 40 μM).…”

Section: Cell Culturementioning

confidence: 99%

Cadmium induces cell centrosome amplification via reactive oxygen species as well as endoplasmic reticulum stress pathway

Zhang

Wang

Lü

et al. 2019

Journal Cellular Physiology

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There is evidence that cadmium can initiate carcinogenesis. However, the underlying mechanisms remain unknown. There is also evidence that moderate centrosome amplification can initiate tumorigenesis. The present study investigated whether cadmium could trigger cell centrosome amplification, and examined the underlying molecular mechanisms. We found that cadmium was able to cause cell centrosome amplification at the subtoxic concentrations, in a dose‐dependent manner. It could cause centrosome amplification via the signaling of reactive oxygen species (ROS). Proteomic analysis revealed that cadmium caused differential expressions of three proteins, which included HSPA1A which is associated with endoplasmic reticulum (ER) stress. Western blot analysis confirmed that cadmium upregulated HSPA1A. Further analyses showed that cadmium upregulated Bip and decreased the phosphorylation of ASK1 as well as increased the phosphorylation of MKK7 and c‐Jun N‐terminal kinases (JNK). Knockdown of JNK2 using small interfering RNA inhibited the cadmium‐induced centrosome amplification but not the level of ROS. N‐acetylcysteine did not inhibit the cadmium‐activated ER stress pathway. In conclusion, our results suggest that cadmium can induce cell centrosome amplification via ROS as well as ER stress through the Bip–TRAF2–ASK1–MKK7–JNK signaling route, in parallel. More studies are required to clarify whether centrosome amplification underlies cadmium‐induced carcinogenesis.

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2D-DIGE and MALDI TOF/TOF MS analysis reveal that small GTPase signaling pathways may play an important role in cadmium-induced colon cell malignant transformation

Cited by 12 publications

References 43 publications

Cadmium Induces Migration of Colon Cancer Cells: Roles of Reactive Oxygen Species, P38 and Cyclooxygenase-2

Cadmium Induces Migration of Colon Cancer Cells: Roles of Reactive Oxygen Species, P38 and Cyclooxygenase-2

Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium-induced cytotoxicity in renal proximal tubular cells

Cadmium induces cell centrosome amplification via reactive oxygen species as well as endoplasmic reticulum stress pathway

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