<i>C. tropicali</i>s promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system

Qu, Junxing; Sun, Zhiheng; Peng, Chen; Li, Daoqian; Yan, Wenyue; Xu, Zhen; Hou, Yayi; Shen, Sunan; Chen, Ping; Wang, Tingting

doi:10.7150/ijbs.59262

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Int J Biol Sci 2021; 17(11):2756-2769. doi:10.7150/ijbs.59262 This issue Cite

Research Paper

C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system

Junxing Qu^1,2, Zhiheng Sun^1,2, Chen Peng^1,2, Daoqian Li^1,2, Wenyue Yan³, Zhen Xu^1,2, Yayi Hou^1,2, Sunan Shen^1,2✉, Ping Chen^3✉, Tingting Wang^1,2✉

1. The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China, 210093.
2. Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, China, 210093.
3. Department of Oncology, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, The First People's Hospital of Yancheng, Yancheng, Jiangsu, China, 224001.

✉ Corresponding authors: Professor Tingting Wang, The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China, 210093. E-mail: wangttedu.cn. Professor Sunan Shen, The State More

Citation:

Qu J, Sun Z, Peng C, Li D, Yan W, Xu Z, Hou Y, Shen S, Chen P, Wang T. C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci 2021; 17(11):2756-2769. doi:10.7150/ijbs.59262. https://www.ijbs.com/v17p2756.htm

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Abstract

Due to chemotherapeutic drug resistance, tumor recurrence is common in patients with colorectal cancer (CRC) and chemo-resistant patients are often accompanied by defects in the mismatch repair system (MMR). Our previous study has shown that Candida tropicalis (C. tropicalis) is closely related to the occurrence and development of colorectal cancer, but whether this conditional pathogenic fungus is involved in chemotherapy needs further investigation. Here we found that C. tropicalis promoted chemotherapy resistance of colon cancer to oxaliplatin. Compared with oxaliplatin-treated group, the expression of functional MMR proteins in tumors were decreased in C.tropicalis/oxaliplatin -treated group, while the glycolysis level of tumors was up-regulated and the production of lactate was significantly increased in C.tropicalis/oxaliplatin -treated group. Inhibiting lactate production significantly alleviated the chemoresistance and rescued the decreased expression of MMR caused by C. tropicalis. Furthermore, we found that lactate down-regulated the expression of MLH1 through the GPR81-cAMP-PKA-CREB axis. This study clarified that C. tropicalis promoted chemoresistance of colon cancer via producing lactate and inhibiting the expression of MLH1, which may provide novel ideas for improving CRC chemotherapy effect.

Keywords: Candida. tropicalis, chemoresistance, glycolysis, lactate, mismatch repair

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APA

Qu, J., Sun, Z., Peng, C., Li, D., Yan, W., Xu, Z., Hou, Y., Shen, S., Chen, P., Wang, T. (2021). C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. International Journal of Biological Sciences, 17(11), 2756-2769. https://doi.org/10.7150/ijbs.59262.

ACS

Qu, J.; Sun, Z.; Peng, C.; Li, D.; Yan, W.; Xu, Z.; Hou, Y.; Shen, S.; Chen, P.; Wang, T. C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int. J. Biol. Sci. 2021, 17 (11), 2756-2769. DOI: 10.7150/ijbs.59262.

NLM

CSE

Qu J, Sun Z, Peng C, Li D, Yan W, Xu Z, Hou Y, Shen S, Chen P, Wang T. 2021. C. tropicalis promotes chemotherapy resistance in colon cancer through increasing lactate production to regulate the mismatch repair system. Int J Biol Sci. 17(11):2756-2769.

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