Cancer metastasis is a process that cancer cells deviate from the primary site and spread to the other areas to form new colonies, which is the leading cause of death in cancer patients. During metastatic progression, circulating cancer cells lodge within the microvasculature of end organs, where most of them die from mechanical deformation. However, cancer cells can survive from mechanical deformation by unknown mechanisms. Recently, Furlow et al.[1] identified a mutation truncated form of pannexin-1 (Panx-1), PANX1 1-89 , which was significantly enriched in highly metastatic cancer cells. PANX1 augmented Panx-1 channel-mediated adenosine triphosphate (ATP) release and enhanced the efficiency of metastasis by promoting metastatic breast cancer cells survival during physical deformation. Additionally, carbenoxolone (CBX), a Panx-1 inhibitor, was proved to reduce the efficiency of breast cancer metastasis. These results suggested that Panx-1 is one of the molecular bases for metastatic cell survival in microvasculature-induced biomechanical trauma [1]. In 2000, three members of pannexins, including Panx-1, Panx-2, and Panx-3, have been found to be new members of gap-junctions' family [2]. Panx-1 was ubiquitously expressed in human tissues. Subsequent studies further revealed that Panx-1 forms single-pass membrane channels that connect the intracellular and extracellular compartments rather than forming intercellular channels spanning the two plasma membranes, which is mainly different from classical gap junctions [3]. Physiologically, Panx-1 channels are mainly involved in the efflux of ATP and regulate cellular inflammasomes [4]. Many studies indicated that Panx-1 is related to epilepsy, neuropathic pain, painful musculoskeletal diseases, ischemia injury, myocardial fibrosis, overactivity of the human bladder, and cancers [5][6][7][8][9][10][11][12][13] (Fig. 1 ).The beneficial or aggravating role of Panx-1 in cancer remains controversial. Lai et al. [5] reported that Panx-1 plays a tumor-suppressive role in vitro and in vivo. Reverse transcription polymerase chain reaction analysis revealed that C6 cells do not express Panx-1. However, stable expression of Panx-1 in C6 glioma cells significantly inhibits cell growth, proliferation, and motility in vitro [5]. Besides, Panx-1 is an important intratumor biomechanical environment regulator that accelerates the dynamic assembly of multicellular C6 glioma aggregates [6]. Panx-1 also significantly reduces the tumor size in athymic nude mice [5,6]. Derangere et al. [7] reported that caspase-1-dependent colon cancer cell pyroptosis is mainly induced through the interaction with Panx-1. These data supported that Panx-1 has a tumorsuppressor property, while some other studies indicated that Panx-1 promotes the development of cancer. Penuela et al. [8] found that Panx-1 is upregulated in B16 melanoma cells rather than in normal melanocytes. Furthermore, Panx-1-depleted B16 melanoma cells exhibit reduced cell migration and growth, resembling normal melanocytes. Knockdown o...