Journal of Cancer Research and Therapeutics

: 2022  |  Volume : 18  |  Issue : 2  |  Page : 488--495

Golgi phosphoprotein 3 promotes ovarian cancer progression and is associated with cisplatin resistance

Teng Liu1, Zhen-Wei Jin2, Ying Li1, Ge Zhang1, Xiao-Ying Yang3, Xiao-Meng Xu1, Ying-Chun Ma2,  
1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University; Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China
2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, P.R. China
3 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong; Weifang Medical University, Clinical medical college, Weifang, Shandong, P.R. China

Correspondence Address:
Ying-Chun Ma
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, No. 16766 Jingshi Road, Jinan, Shandong
P.R. China


Background: Golgi phosphoprotein-3 (GOLPH 3) is involved in the development of several human cancers. However, the clinical significance and biological role of GOLPH 3 in ovarian cancer (OC) remains unknown. Methods: The expression of GOLPH 3 in OC cell lines was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The role of GOLPH 3 in tumorigenicity, migration, and invasion of OC cell lines by small interference RNA, scratch wound-healing assays, and transwell assays was detected. In addition, western blotting was used to determine whether GOLPH 3 is associated with the PI3K/AKT/mTOR signaling pathway. Furthermore, RT-qPCR verified whether GOLPH 3 is associated with drug resistance. Results: GOLPH 3-positive expression rate was higher in OC. Downregulation of GOLPH 3 markedly inhibited the migration and invasion and may be related to the PI3K/AKT/mTOR signal pathway. Moreover, the result of the experiment proved that GOLPH 3 enhances the sensitivity of OC to cisplatin by regulating ATP7A/B. GOLPH 3 promoted the invasion and migration of OC, and the mechanism may be related to the PI3K/Akt/mTOR pathway. In addition, inhibition of GOLPH 3 increased the sensitivity of OC cells to cisplatin, which may be associated with ATP7A/B. Conclusion: This study found that GOLPH3 may promote the migration and invasion of OC cells through PI3K/Akt/mTOR pathway. At the same time, low expression of GOLPH3 increased the sensitivity of OC cells to cisplatin.

How to cite this article:
Liu T, Jin ZW, Li Y, Zhang G, Yang XY, Xu XM, Ma YC. Golgi phosphoprotein 3 promotes ovarian cancer progression and is associated with cisplatin resistance.J Can Res Ther 2022;18:488-495

How to cite this URL:
Liu T, Jin ZW, Li Y, Zhang G, Yang XY, Xu XM, Ma YC. Golgi phosphoprotein 3 promotes ovarian cancer progression and is associated with cisplatin resistance. J Can Res Ther [serial online] 2022 [cited 2022 Nov 30 ];18:488-495
Available from:

Full Text


Ovarian cancer (OC) remains a significant health problem for women, and it is the most lethal gynecologic cancer.[1],[2] Epithelial ovarian cancer (EOC) is the most common type of OC, accounting for 85%–90% of serous OC cases.[3] Unfortunately, due to the lack of effective screening methods, about 67% of OC patients are advanced, have a high recurrence, and quickly produce drug resistance.[4],[5],[6] Thus, there is a substantial need to develop new biomarkers to enable diagnosis at earlier stages and targeted therapies to achieve better treatment.

Golgi phosphoprotein-3 (GOLPH 3), also known as GPP34/GMx33/MIDAS, and inhuman chromosome 5p13, is a highly conserved protein with a molecular weight of 34 KD.[7] Located on the surface of the Golgi apparatus, GOLPH 3 is involved in Golgi homeostasis and vesicle transport.[8] Previous studies have shown that GOLPH 3 is highly expressed in a variety of tumors, such as lung cancer,[9] colorectal cancer,[10] and gastric cancer.[11] Additionally, it was found that overexpressed GOLPH 3 promotes tumor proliferation and migration, related to the tumor's clinical stage and poor prognosis. In previous studies,[12],[13] the expression of GOLPH 3 protein in OC tissue was evaluated using immune-histochemistry. It was discovered that overexpression of GOLPH 3 protein is associated with a worse prognosis in patients with EOC. This study can fill the gap in the study of the mechanism of GOLPH 3 promoting tumorigenesis. PI3K/AKT/mTOR signaling pathway is associated with tumor cell proliferation, apoptosis, and invasion in various cancers.[14],[15],[16] More importantly, it has been reported that GOLPH 3 inhibition reverses oxaliplatin resistance of colon cancer cells via the suppression of the PI3K/AKT/mTOR pathway. Thus, we speculate that GOLPH 3 may play an oncogene role through PI3K/AKT/mTOR in OC.

This study explored the role of GOLPH 3 in the migration and invasion of OC cells and confirmed the relationship between GOLPH 3 and PI3K/AKT/mTOR axis and apoptosis in SKOV3 and A2780 cells by western blot assays. In addition, the relationship between GOLPH 3 and cisplatin sensitivity was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Together, these results suggested that GOLPH 3 has the potential as a novel diagnostic biomarker and therapeutic target for the treatment of human OC.

 Materials and Methods

Cell lines and cell culture

The human normal ovarian epithelial cells, IOSE80 (ATCC, Manassas, VA, USA, and human OC cell lines A2780 and SKOV3 (ATCC, Manassas, VA, USA), were cultured in RPMI 1640 medium (Gibco, USA). They were supplemented with 10% fetal bovine serum (FBS) (Hyclone, USA) at 37°C and 5% CO2 humidity incubator. We were approved by the Ethics Committee on April 02, 2021(Ethics, S879).

Transient interference assays

Small interfering RNA (siRNA) was obtained from Invitrogen (USA) and Ribobio (Guangzhou, China). About 2 × 105 cells per well were inoculated in a 6-well plate and cultured to about 50% cell density; then, serum-free RPMI1640 was used instead of the medium. A mixture of siRNA and liposome 2000 (Invitrogen, Carlsad, CA) was added to the cell based on the manufacturer's instructions. After incubation for 4 h, they were cultured in the RPMI1640 medium supplemented with 10% fetal bovine serum. The siRNA sequences used in this study were as follows: GOLPH 3, sense, 5'-GGCCAACACCAAUGAGGUUTT-3'; antisense, 5'- AACCUCAUUGGUGUUGGCCTT-3'; Negative control, sense, 5'-UUCUCCGAACGUGUCACGUTT-3'; antisense, 5'-ACGUGACACGUUCGGAGAATT-3'.

RT-qPCR assays

Total RNA was isolated from each sample and cultured cells by using TRNzol reagent (Invitrogen, CA, USA). An additional DNase digestion procedure was included in the isolation of RNA to remove contaminating DNA and was performed according to the manufacturer's protocol. cDNA was synthesized using a First Strand cDNA Synthesis kit (Fermentas, Thermo Scientific, EU). qPCR was performed using SYBR Premix Ex Taq II (TaKaRa), and GAPDH was used as an internal control,then was performed using AriaMx Real-Time PCR (7300 Sequence Detection System, Applied Biosystems). The primer sequences used for each target gene were as follows: GOLPH 3, sense, 5'-ACATCCCCTCACCAATAACAAC-3'; antisense, 5'-TAGCCAAATCATACTGCTCGTC-3'; GAPDH, sense, 5'-GGTATCGTCGAAGGACTCATGAC-3'; antisense, 5'-ATGCCAGTGAGCTTCCCGTTCGC-3'. RT-qPCR was run at 95°C for 15 min followed by 40 cycles of 95°C for 10 s, 55°C for 30 s, and 72°C for 30 s. Data were collected during the cycles at 72°C. Relative gene expression was calculated using the comparative Ct method. All experiments were performed in triplicate.

Scratch wound-healing assays

The ability of migration in transfected cells was evaluated by scratch wound-healing. At about every 0.5–1 cm, a marker pen was used to draw three horizontal lines on the back of the 6-hole plate. About 5 × 105 cells were added to each hole. The ruler was compared with the head of the gun, and the horizontal line on the back was scratched. The cells were washed with PBS three times and then cultured in a medium with low serum. The initial distance at 0 h and the residual gap length at 24 h and 48 h after scratching were observed microscopically at a magnification (40×).

Migration and invasion assays

Matrigel diluted in serum-free culture medium (1:4) was inserted into the 24-well transwell plates (BD Biosciences) for transwell migration assays for coating the polycarbonate membranes. Cells were diluted by RPMI 1640 supplemented with 1% fetal bovine serum (FBS). Next, 1 × 105 cells were added to the top chambers of 24-well transwell plates, and completed media were added to the bottom chambers. After 24-h incubation, non-migrated cells at the top were removed, and migrated cells at the bottom were fixed, stained, and counted.

A similar approach but without Matrigel coating was used cell migration assays, and 2 × 105 cells were planted.

CCK8 assays

Cell viability was measured by cell counting kit-8 (CCK8). The cells were seeded into 96-well plates with 10 μL of CCK8 reagent in every well, and there were 4 × 104 cells in each well, all incubated at 37°C for 1 h. The optical density (OD) values were measured at 450-nm wavelength by Multiskan FC (Thermo Fisher Scientific, Inc.).

Flow cytometer analysis

Annexin V-FITC Apoptosis Detection Kit (Biyuntian, China) was used to detect the apoptotic ability of OC cells according to the manufacturer's instructions. After 48 h of transfection, the cells were washed by PBS, fixed with 70% ethanol at 4°C, and then stained with PI, and the apoptosis was detected by flow cytometry (FCM, BD Biosciences).

Western blot assays

The expression of GOLPH 3, mTOR, p-mTOR, PI3K, P-PI3K, AKT, p-AKT, BCL-2, and BAX was detected using western blot assays. First, the frozen specimen tissues were weighed, and 20 mg of tissue was extracted by adding 100 μL of ice-cold cell lysis buffer (Beyotime, Jiangsu, China), including PMSF (Beyotime, Jiangsu, China), crushed by using gentle MACSTM single-cell processor (Miltenyi Biotec, Germany) until the full cleavage 12000-g centrifuge for 5 min; then, the supernatant was taken and subsequent operation was carried out. Next, cells were washed twice with ice-cold phosphate-buffered saline (PBS) and the previous method was used to collect total protein.

The protein concentration was determined by BCA Protein Assay Kit (Beyotime Biotechnology, Jiangsu, China). Next, 50 μg of protein samples were separated on 10% SDS-PAGE and transferred to PVDF membranes (Millipore). After blocking 5% nonfat milk in Tris-buffered saline containing 0.1% Tween-20 (TBST) for 1 h at room temperature, membranes were incubated with anti-polyclonal rabbit anti-GOLPH 3 antibody, anti-PI3K antibody, anti-P-PI3K antibody, anti-AKT1 antibody, anti-P-AKT antibody, anti-mTOR antibody, anti-P-mTOR antibody, anti-BCL-2 antibody, anti-BAX antibody (Abcam, USA), and GAPDH antibody (Beyotime Biotechnology, Jiangsu, China) for 4°C overnight. After washing with TBST three times, the membranes were incubated with goat anti-rabbit secondary antibodies (Beyotime Biotechnology, Jiangsu, China) for 1 h The bands were detected using ECL Western blotting kit (Beyotime Biotechnology, Jiangsu, China). The densities of bands were measured using a densitometer and analyzed with Quantity One analysis software (Bio-Rad, USA).

Statistical analysis

All statistical analyses were conducted using Graphpad Prism 8.0.1. (244) Values were expressed as means ± SD. Comparison of data was analyzed by t test. The dose-response curve was used to analyze the half-maximal inhibitory concentration (IC50). P < 0.05 was considered statistically significant in all cases.


High expression of GOLPH 3 in OC cell lines

A previous study[12] discovered that GOLPH 3 was highly expressed in OC tissue by immunohistochemical assays. This study used RT-qPCR and western blot assays to detect the mRNA and protein level of GOLPH 3 in cells. As shown in [Figure 1]a and [Figure 1]b, compared with normal ovarian epithelial cells (IOSE80), the mRNA and protein level of GOLPH 3 in SKOV3 and A2780 cell lines were higher. Furthermore, as shown in [Figure 1]c, [Figure 1]d, [Figure 1]e, the transfection efficiency of si-GOLPH 3-3 was the highest, and si-GOLPH 3-3 was used in the follow-up experiment.{Figure 1}

GOLPH 3-facilitated migration and invasion of OC cells

To explore the functions of GOLPH 3, we used transwell assays to detect the migration and invasion ability of cells after knocking down GOLPH 3. As shown in [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, the number of cells migrated and invaded in the si-GOLPH 3-3 group was significantly lower than that in the mock and si-NC groups. In addition, we verified the effect of GOLPH 3 on the migration of OC cells through scratch wound-healing assays [Figure 2]e, [Figure 2]f, [Figure 2]g, [Figure 2]h. Compared with the si-NC, the migration of the si-GOLPH 3-3 group decreased. Therefore, inhibition of GOLPH 3 can significantly reduce the invasion and migration ability of SKOV3 and A2780 cells.{Figure 2}

GOLPH 3 is associated with the PI3K/AKT/mTOR signal pathway, and apoptosis is determined in OC cells

To further study the role of GOLPH 3 in OC, the effects of differential expressions of GOLPH 3 on the PI3K/AKT/mTOR axis were analyzed by western blot assays. We examined the expression of key molecules involved in the PI3K/AKT/mTOR pathway. A rescue experiment was adopted to assess further that inhibition of GOLPH 3 inhibited the PI3K/AKT/mTOR pathway. The si-GOLPH 3-3 group significantly decreased the levels of phosphorylated mTOR, phosphorylated PI3K, and phosphorylated AKT protein in SKOV3 and A2780 cells [Figure 3]a. In addition, to deal with the si-GOLPH 3-3 group, 740 Y-P, a PI3K agonist, was used. It was discovered that 740 Y-P restored downregulation of key molecules that inhibit the GOLPH 3-induced PI3K/AKT/mTOR pathway. The above results suggest that the inhibition of GOLPH 3 can inhibit the PI3K/AKT/mTOR axis of OC cells. It is generally believed that PI3K/Akt/mTOR plays a vital role in apoptosis; thus, the relationship between GOLPH 3 and apoptosis was explored. Western blot assays were used to detect apoptosis-related proteins BAX and BCL-2. The results showed that the inhibition of GOLPH 3 can upregulate the expression of BAX and inhibit the expression of BCL-2. However, 740 Y-P reversed the inhibitory effect of GOLPH 3 on apoptosis of SKOV3 and A2780 cells [Figure 3]a. Further FCM analysis compared with the si-NC group showed that downregulation of GOLPH 3 promoted the apoptosis of OC cells, and cotransfection of 740 Y-P reversed the apoptosis rate induced by inhibition of GOLPH 3 [Figure 3]b. To sum up, knocking down GOLPH 3 may induce ovarian cell apoptosis by downregulating the PI3K/AKT/mTOR axis, which may be one of its regulatory mechanisms.{Figure 3}

GOLPH 3 reduced the sensitivity of OC cells to cisplatin

CCK8 assays detected the cell viability, and RT was used to detect the expression level of GOLPH 3-qPCR to assess whether GOLPH 3 affects the sensitivity of OC cells to cisplatin. We found that the inhibitory effect of cisplatin on the viability of SKOV3 and A2780 cells increased with an increase in the cisplatin concentration (0, 1, 2, 4, 8, 16, and 32 μg/mL) [Figure 4]a, [Figure 4]b. Conversely, the expression of GOLPH 3 decreased at the mRNA level with an increase in the cisplatin concentration [Figure 4]c, [Figure 4]d. In addition, according to the result of the IC50 test on SKOV3 and A2780 cells treated with cisplatin [Figure S1], we used IC50 cisplatin concentration to treat SKOV3 cells (15.05 μg/mL) and A2780 cells (7.911 μg/mL), respectively. The results showed that the cell survival rate of the si-OLPH 3-3 group was lower than that of the si-NC group [Figure 4]e, [Figure 4]f, which further confirmed that GOLPH 3 is involved in the regulation of cisplatin sensitivity in OC cells.{Figure 4}[INLINE:1]

Knocking down GOLPH 3 can downregulate the expression of ATP7A/B

To further investigate how GOLPH 3 regulates cisplatin sensitivity in OC, the expression level of ATP7A/B by RT-qPCR was detected. Studies have shown that ATP7A/B pumps platinum antineoplastic drugs in OC and plays a vital role in chemotherapy resistance. As shown in [Figure 5], RT-qPCR assays revealed that ATP7A/B were less expressed in the si-GOLPH 3-3 group compared with mock and si-NC groups. Therefore, it was speculated that GOLPH 3 might regulate cisplatin sensitivity by regulating ATP7A/B.{Figure 5}


OC is the second-highest cancer incidence in women, with the highest mortality rate of gynecological malignant tumors, a severe threat to women's lives and health.[17] The occurrence and invasion of OC is a complex process regulated by various related genes.[18] GOLPH 3 is a peripheral membrane protein located in the Golgi body and its vesicles, which plays a role in tumor formation, development, and metastasis.[19] This study found that GOLPH 3 was highly expressed in OC cell lines and related to tumor resistance. The basis for OC's clinical diagnosis, treatment, and prognosis is provided.

Previous studies[12],[13] used immunohistochemical assays to find that GOLPH 3 immunostaining was located in the cytoplasm in two ways. They condensed into large particles, showed perinuclear distribution, and scattered fine particles in the cytoplasm. Overexpression of GOLPH 3 protein was associated with poor prognosis in patients with epithelial ovarian cancer (EOC). In addition, GOLPH 3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis.[20] The mechanism of GOLPH 3 in the progress of OC was further studied. Evidence showed that GOLPH 3 is involved in various biological behaviors of tumors. GOLPH 3 promoted the proliferation and invasion of gastric cancer cells. It promoted the progress of EMT by inhibiting the expression of E-cadherin and inducing the expression of vimentin and N-cadherin.[21] GOLPH 3 also promotes the migration and invasion of tumor cells.[22] Consistent with previous studies, transwell assays and scratch wound-healing assays were used to show that cell migration and invasion ability in the si-GOLPH 3-3 group was significantly higher than that in the si-NC group. To sum up, GOLPH 3 promoted the invasion and migration of OC.

Moreover, the PI3K/AKT/mTOR signal pathway is a complex signal transduction pathway that plays an important role in regulating cell growth and differentiation and tumor occurrence, development, and metastasis.[23],[24],[25] For example, it has been found that 740 Y-P can promote the growth of hepatocellular carcinoma cells by activating the PI3K/AKT signal pathway.[26] Another study found that 740 Y-P activated the PI3K/AKT signal pathway to promote the proliferation and migration of gastric cancer and inhibit apoptosis.[27] This research found that the phosphorylation levels of PI3K, Akt, and mTOR proteins in the GOLPH 3 knockout group were significantly decreased. In contrast, the expression of apoptotic protein BAX was upregulated, and anti-apoptotic protein BCL-2 was downregulated. Thus, a series of effects caused by knocking down GOLPH 3 can be reversed after using 740 Y-P. It was further confirmed that inhibiting the expression of GOLPH 3 can promote the apoptosis of OC cells by FCM analysis, and the effect of silencing GOLPH 3 on apoptosis was reversed by PI3K agonist 740 Y-P. Thus, it was assumed that the overexpression of GOLPH 3 in OC inhibits tumor cell apoptosis by activating PI3K/AKT/mTOR, which may be one of its mechanisms.

Previous studies found that the diffuse or condensed expression of GOLPH 3 was related to the morphology of the Golgi apparatus and chemotherapy resistance. Moreover, it has been reported that GOLPH 3 is associated with cisplatin sensitivity in bladder cancer,[28] lung cancer,[9] OC,[29] and colon cancer.[30] Inhibition of GOLPH 3 expression can reverse cisplatin resistance, consistent with the results of this study. Furthermore, it was found that silencing GOLPH 3 can further inhibit cell viability compared with cisplatin-treated cancer cells. ATP7A and ATP7B, located in the trans-Golgi matrix, are involved in regulating the exocytosis of platinum antineoplastic drugs.[31],[32] It has been reported that ATP7A/B may promote cisplatin efflux by mediating Golgi vesicle transport, thus reducing the concentration of platinum in tumor cells and participating in cisplatin resistance in tumor cells.[33] Moreover, it has been reported that GOLPH 3 promotes the Golgi apparatus to release vesicles by binding to MYO18A.[19] In the study, with the inhibition of GOLPH 3, the expression of ATP7A/B also decreased. At present, there are no reports on the specific regulatory relationship between GOLPH 3 and ATP7A/B. This study focused on the basic function of GOLPH 3 in OC and the preliminary exploration of the regulatory relationship with drug resistance genes. Due to the lack of experimental energy, the specific regulatory mechanism of GOLPH 3 and ATP7A/B will be focused on in our next study.


The results revealed that GOLPH 3 promotes the invasion and migration of OC. In addition, it participates in the inhibition of apoptosis of OC cells by promoting the PI3K/AKT/mTOR signal pathway. Moreover, it participates in regulating cisplatin sensitivity by regulating ATP7A/B. We believe that GOLPH 3 is a potential gene target for preventing and treating EOC.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Sehouli J, Braicu E, Richter R, Denkert C, Jank P, Jurmeister P, et al. Prognostic significance of Ki-67 levels and hormone receptor expression in low-grade serous ovarian carcinoma: An investigation of the Tumor Bank Ovarian Cancer Network. Hum Pathol 2019;85:299-308.
2Liu L, Pang Y, Zhao X, Li R, Jin C, Xue J, et al. Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells. Arch Gynecol Obstetr 2019;299:1627-39.
3Alrashed M, Ahmad M, Yongmei W, Xiuyeng W. Differential expression of miR-130a-3p modulate ovarian epithelial carcinoma (OEC) cell development and could be a biomarker for OEC. J Reprod Immunol 2021;145:103310.
4Ziebarth A, Landen C, Alvarez R. Molecular/genetic therapies in ovarian cancer: Future opportunities and challenges. Clin Obstetr Gynecol 2012;55:156-72.
5Bortot B, Mongiat M, Valencic E, Dal Monego S, Licastro D, Crosera M, et al. Nanotechnology-based cisplatin intracellular delivery to enhance chemo-sensitivity of ovarian cancer. Int J Nanomedicine 2020;15:4793-810.
6Sad L, Mohamed D, Elanwar N, Elkady A. CXCR4 and RIF1 overexpression induces resistance of epithelial ovarian cancer to cisplatin-based chemotherapy. J Cancer Res Ther 2021;17:1454-61.
7Scott K, Chin L. Signaling from the Golgi: Mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis. Clin Cancer Res 2010;16:2229-34.
8Sechi S, Frappaolo A, Karimpour-Ghahnavieh A, Piergentili R, Giansanti M. Oncogenic roles of GOLPH 3 in the physiopathology of cancer. Int J Mol Sci 2020;21:933.
9Zhao C, Zhang J, Ma L, Wu H, Zhang H, Su J, et al. GOLPH 3 promotes angiogenesis of lung adenocarcinoma by regulating the Wnt/β-catenin signaling pathway. Onco Targets Ther 2020;13:6265-77.
10Zheng X, Shi Z, Qiu C, Hong Z, Wang C, Zhuang H, et al. Protosappanin B exerts anti-tumor effects on colon cancer cells via inhibiting GOLPH 3 expression. Integr Cancer Ther 2020;19:1534735420972477.
11Wang C, Zhuang H, Shi Z, Qiu C, Chen Z, Tang L. Golgi phosphoprotein 3 represents a novel tumor marker for gastric and colorectal cancers. Dis Markers 2021;2021:8880282.
12Ma Y, Ren Y, Zhang X, Lin L, Liu Y, Rong F, et al. High GOLPH 3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma. Virchows Arch 2014;464:443-52.
13Ma Y, Wang X, Wu Y, Sun B, Lv H, Rong F, et al. Overexpression of GOLPH 3 protein is associated with worse prognosis in patients with epithelial ovarian cancer. Tumour Biol 2014;35:11845-9.
14Huang J, Liu C, Duan S, Lin J, Luo Y, Tao S, et al. Gigantol inhibits proliferation and enhances DDP-induced apoptosis in breast-cancer cells by downregulating the PI3K/Akt/mTOR signaling pathway. Life Sci 2021;274:119354.
15Chen H, Feng X, Gao L, Mickymaray S, Paramasivam A, Abdulaziz Alfaiz F, et al. Houttuynia cordataInhibiting the PI3K/AKT/mTOR signalling pathway with copper oxide nanoparticles from plant: Attenuating the proliferation of cervical cancer cells. Artif Cells Nanomed Biotechnol 2021;49:240-9.
16Wei J, Zhang X, Pan H, He S, Yuan B, Liu Q, et al. Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway. Oncol Lett 2021;21:332.
17Zhang X, Xu S, Hu C, Fang K, Zhou J, Guo Z, et al. LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression. Bioch Biophys Res Commun 2020;533:1039-47.
18Lee K, Seifert B, Shimelis H, Ghosh R, Crowley S, Carter N, et al. Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels. Genet Med 2019;21:1497-506.
19Kuna R, Field S. GOLPH 3: A Golgi phosphatidylinositol (4) phosphate effector that directs vesicle trafficking and drives cancer. J Lipid Res 2019;60:269-75.
20Rizzo R, Russo D, Kurokawa K, Sahu P, Lombardi B, Supino D, et al. Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH 3. EMBO J 2021;40:e107238.
21Ouyang J, Song F, Li H, Yang R, Huang H. miR-126 targeting GOLPH 3 inhibits the epithelial-mesenchymal transition of gastric cancer BGC-823 cells and reduces cell invasion. Eur J Histochem 2020;64:3168.
22Sun J, Yang X, Zhang R, Liu S, Gan X, Xi X, et al. GOLPH 3 induces epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway in epithelial ovarian cancer. Cancer Med 2017;6:834-44.
23Makwana V, Rudrawar S, Anoopkumar-Dukie S. Signalling transduction of O-GlcNAcylation and PI3K/AKT/mTOR-axis in prostate cancer. Biochim Biophys Acta Mol Basis Dis 2021;1867:166129.
24Han C, Chen S, Ma H, Wen X, Wang Z, Xu Y, et al. RPN2 predicts poor prognosis and promotes bladder cancer growth and metastasis via the PI3K-Akt pathway. Onco Targets Ther 2021;14:1643-57.
25Qian H, Huang T, Chen Y, Li X, Gong W, Jiang G, et al. X-linked inhibitor of apoptosis protein inhibitor Embelin induces apoptosis via PI3K/Akt pathway and inhibits invasion in osteosarcoma cells. J Cancer Res Ther 2018;14:S648-55.
26Li M, Sun P, Dong K, Xin Y, TaiLulu A, Li Q, et al. Chemerin reverses the malignant phenotype and induces differentiation of human hepatoma SMMC7721 cells. Arch Pharm Res 2021;44:194-204.
27Ma F, An K, Li Y. Silencing of long non-coding RNA-HCG18 inhibits the tumorigenesis of gastric cancer through blocking PI3K/Akt pathway. Onco Targets Ther 2020;13:2225-34.
28Zhang Q, Zhuang J, Deng Y, Yang L, Cao W, Chen W, et al. miR34a/GOLPH 3 axis abrogates urothelial bladder cancer chemoresistance via reduced cancer stemness. Theranostics 2017;7:4777-90.
29Niu L, Ni H, Hou Y, Du Q, Li H. miR-509-3p enhances platinum drug sensitivity in ovarian cancer. Gene 2019;686:63-7.
30Zhou Z, Wang L, Hong Z, Qiu C, Wang M, Chen Z, et al. Silencing GOLPH 3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways. Int J Oncol 2018;53:1183-92.
31Cerovska E, Elsnerova K, Vaclavikova R, Soucek P. The role of membrane transporters in ovarian cancer chemoresistance and prognosis. Expert Opin Drug Metab Toxicol 2017;13:741-53.
32Vyas A, Duvvuri U, Kiselyov K. Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity. Biochem J 2019;476:3705-19.
33Sudhahar V, Das A, Horimatsu T, Ash D, Leanhart S, Antipova O, et al. Copper transporter ATP7A (copper-transporting P-Type ATPase/Menkes ATPase) limits vascular inflammation and aortic aneurysm development: Role of MicroRNA-125b. Arterioscler Thromb Vasc Biol 2019;39:2320-37.