The Role and Therapeutic Potential of Macropinocytosis in Cancer

Zejing Qiu; Wencheng Liu; Qianru Zhu; Kun Ke; Qicong Zhu; Weiwei Jin; Shuxian Yu; Zuyi Yang; Lin Li; Xiaochen Sun; Shuyi Ren; Yanfen Liu; Zhiyu Zhu; Jiangping Zeng; Xiaoyu Huang; Yan Huang; Lu Wei; Mengmeng Ma; Jun Lu; Xiaoyang Chen; Yiping Mou; Tian Xie; Xinbing Sui

doi:10.3389/fphar.2022.919819

The Role and Therapeutic Potential of Macropinocytosis in Cancer

Front Pharmacol. 2022 Aug 15:13:919819. doi: 10.3389/fphar.2022.919819. eCollection 2022.

Authors

Zejing Qiu^{1

2}, Wencheng Liu^{1

2}, Qianru Zhu^{1

2}, Kun Ke³, Qicong Zhu³, Weiwei Jin³, Shuxian Yu^{1

2}, Zuyi Yang^{1

2}, Lin Li^{1

2}, Xiaochen Sun^{1

2}, Shuyi Ren^{1

2}, Yanfen Liu^{1

2}, Zhiyu Zhu^{1

2}, Jiangping Zeng^{1

2}, Xiaoyu Huang^{1

2}, Yan Huang^{1

2}, Lu Wei^{1

2}, Mengmeng Ma^{1

2}, Jun Lu^{1

2}, Xiaoyang Chen^{1

2}, Yiping Mou³, Tian Xie^{1

2}, Xinbing Sui^{1

2}

Affiliations

¹ Department of Medical Oncology and School of Pharmacy, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China.
² Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, China.
³ Department of Gastrointestinal-Pancreatic Surgery, General Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Abstract

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Keywords: anticancer therapies; macropinocytosis; methuosis; promoting cancer growth; tumor microenvironment.

Publication types

Review